22
1 UNIVERSITY OF PRETORIA Creation of a National Compound Library/Biodiversity Market Bank Prof Vinesh Maharaj November 2015

Creation of a National Compound Library/Biodiversity ... · Creation of a National Compound Library/Biodiversity Market Bank ... knowledge system on the medicinal use of these plants,

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Citation preview

Page 1: Creation of a National Compound Library/Biodiversity ... · Creation of a National Compound Library/Biodiversity Market Bank ... knowledge system on the medicinal use of these plants,

1

UNIVERSITY OF PRETORIA

Creation of a National Compound

LibraryBiodiversity Market Bank

Prof Vinesh Maharaj

November 2015

Sources of Drugs

52 of all drugs has some

relation to natural compounds

3

South African plants of

commercial interest

Agathosma betulina (Buchu) Aloe ferox

Artemisia afra (Umhlonyane) Aspalathus

linearis (Rooibos tea) Cyclopia genistoides

Harpagophytum procumbens (Devils Claw)

Hoodia gordonii Hypoxis hemerocallidea

Lippia javanica (Musukudu)

Mesembryanthemum tortuosum (kougoed)

Pelargonium sidoides Siphonochilus

aethiopicus (indungulo) Sutherlandia

frutescens Warburgia salutaris (isihaha) and

Xysmalobium undulatum (ishongwe)

B-E vanWyk Journal of Ethnopharmacology 119 (2008) 342ndash355

hellip but which plant to

choose and how to

proceed

Research Methodology

Bio-guided essays

Random Approach

Chemo-taxonomical

Approach

Ethno-botanical

Approach

4

Bio-guided essays

Need to identify the active molecules

bull Biological tests sophisticated

bull Regulatory ndash QC standardization

check for aldulteration

11

Yes

Bio testsIsolation

amp

Purification

Preparative

HPLC

Extracts from various

solvents

Extraction

amp

Fractionation

Bio-essay on

each fraction

Screening

Bioactive NPs

No

Useless fraction

(discarded)

Further

fractionationsIs the fraction

Active

Structure

Elucidation

NMR UV IR CD

Oxydative

degradation

Screening flowchart investigation for bioactive compounds

Classical Research Methodology

6

Challenges

bull Genetic material may have 100rsquos compounds

bull Highly complex

bull Contain artefacts

bull Losses in purification

bull Old methods need large quantities of raw material eg plants

bull Long times to isolate one compound pure determine

structure ndash 6 to 12 months

bull Testingscreening of extracts no longer relevant

Storage

Compounds

7

Most common phrase used in most proposals to fund research based on

Biodiversity and IKS in SA

ldquoDespite having a vast reserve of botanical specimens and a strong indigenous

knowledge system on the medicinal use of these plants South Africa is yet to

launch major registered medicines or drugs based on South African plants into

the local and international biotechnology and pharmaceutical arenardquo

Are we delivering leadsproducts at sufficient rate based on our biodiversity

Possible explanations

bull Emphasis on botanical products difficulties in further development with lack

of regulations

bullNon-Functional interface between Natural products MedChem and Biologists

bullDevelopment cycles in complete ndash lack of co-ordinated and collaborative

research ndash ldquoJohn Wayne syndromerdquo

bullIP ownership

bullLack of assessment of SA chemical diversity ndash fragmented libraries

repositories of samples

bullInability to do high through put purification and structure elucidation of

natural compounds

Further Challenges

bull Academic environment biodiversity samples leave country for research

with limited value addition

bull Fragmented access to local biodiversity

bull No tracking system non coordinated access

bull Local collection not in formats ready for high end and HT

ldquoscreeningtestingrdquo

bull No local ldquoclearing houserdquo to provide trusted collections

bull Government approved and compliance

bull High quality preserved and reproducible

The Challenge in Drug Discovery

Possible Solutions

a) Increase Number of candidate compounds

b) Increase Quality of candidate compounds eg Natural products

Local and International perspectives

Several International InstitutesProgrammes

bull National Cancer Institute (US)

ndash Over 100 000 natural extracts and compounds

ndash Samples collected around the world

ndash Most successful in using these to develop cancer drugs eg taxol vinca

alkaloids

bull South Korea

ndash Govt set up KRIBB

ndash Create natural product libraries

bull Several natural product institutes in China

ndash Repositories of samples

bull Eskitis Institute ndash Australia

bull Novartis - Switzerland

10

Nature Bank

We have a long-term vision for the sustainable use of biodiversity

for the next century and beyond

45000 biota

samples

Plants marine invertebrates from

Australia China PNG

Extracts of biota

Our work with industry has taught us

how to retain only the drug-like

components

200000 Optimised

Nature Bank

fractions

Nature Bank is ready and available for

collaborations with industry academic

groups and PPPs

Fragment Library

Compounds

Scaffold Library

Compound Library

350000 pure compounds

200000 natural product fractions

Cherry-picking

Automated formatting into microtitre plates

Example

Eskitis Institute

bull Own collections

bull Deposited

collections eg

Univ Councils

Other Australia

Univ deposits

100k samples

Formatting and

dispatch

Univ requests

screening of 50k

of their samples

with Pharma

Pharma receives

samples

bull Eskitis weighs and

prepares samples

bull Dispatches

bull Govt is lsquonotifiedrdquo

Local and

International

requests

Our TargetsCreation of a diverse library of natural extracts fractions and chemical

compounds endowed with biological activity and to be used research

programs in a sustainable manner

Extracts

bull Generation of hundreds of

thousands of fractions

bull Structure elucidation of pure

compounds

bull Database for fractions and

compounds

bull Purity storage and format

compatible with HTS

operations

HT

separation

bull Plants

bull Micro-organisms

bull Marine

National Strategy and TargetCreation of a diverse library of natural samples and chemical compounds

endowed with biological activity to be used in research programs in a

sustainable manner

Storage and

Database

Extracts

Plant extract

Clean up

Pre-fractionated extract

Inject

Prep LC

UV

MS

Liquid handler

NMR

DNP AntibaseStructure elucidation taxonomy bioassay data

Information management system

COOH

OO

O

HO

HO

O

O

OH

OH

OH

H3CO

O

O

Chemical Formula C3H3O3bull

Exact Mass 8701

Chemical Formula C25H23O12bull

Exact Mass 51512

Sample Storage

Sample Administration

System

Compounds in vials

Genvac evap

Database

TQD MS

The nuts and bolts

Leveraging the Library ndashConservation

bull Trusted collection

ndash No need to recollect samples

ndash Legal controlled access to industry acedemia

ndash Link to IK databases (NIKMAS)

ndash Link to plant distribution maps

ndash One ldquoshop stoprdquo to the world eg pharma

ndash Control of samples leaving the country

ndash Tool for issuing notifications and permits

bull HCD

ndash New skills training for post graduates

bull Food and cosmetics

ndash Growing market for natural ingredients

1717

Possible Model for the Market

bank

National Repository of Biodiversity samples and

Natural Compounds

bull Legal entity

bull Hosted or independent

bull Government control and access

bull Compound production and storage

bull Core Staff

bull Students

Access

Ownership

Science

Councils

Communities

NGOsUniversities

Deposit

samples

Leveraging the Library ndash Health needs

bull Burden of disease in SA

ndash HIV

ndash TB

ndash Cancer

ndash Cardiovascular disease

ndash Diabetes

ndash Malaria

ndash Alzheimerrsquos

bull Life style diseases

ndash Obesity

bull Food and cosmetics

ndash Growing market for natural ingredients

18

Leveraging the Library Socio-economic

bull Local ldquoclearing houserdquo to provide trusted collections

ndash Government approved and compliance

ndash High quality preserved and reproducible

ndash Controlled access

bull Conservation

ndash No need for huge plants collections

bull Agro-processing

ndash Cultivation and processing through local communities

bull IP creation owned by South Africans

ndash Chemical composition

bull Human Capital Development - skills

bull Economic benefits

ndash Commercialization through Licensing

ndash Local Manufacturing

ndash Access fees19

Thank you

Discussion

21

Structure determination of

molecules

bull NMR

bull MS

bull UV IRCD

copy CSIR 2008 wwwcsircozacopy CSIR 2008 wwwcsircoza

HPLC

pumpHPLC column

INJECTION

- Extract

- Fraction

- Mixture

LCMS

INTERFACE

Splitting dependent

of the LCMS

interfaces used

waste

UV

MS

UV

MS

spectra

1

Speed vac -

off-line or on-line

biological assays

2- LCmicro fractionation

Active fractionsemi

pure compounds

Speed vac -

Storage

Structural

information

Separation by HPLCUVMS

Page 2: Creation of a National Compound Library/Biodiversity ... · Creation of a National Compound Library/Biodiversity Market Bank ... knowledge system on the medicinal use of these plants,

Sources of Drugs

52 of all drugs has some

relation to natural compounds

3

South African plants of

commercial interest

Agathosma betulina (Buchu) Aloe ferox

Artemisia afra (Umhlonyane) Aspalathus

linearis (Rooibos tea) Cyclopia genistoides

Harpagophytum procumbens (Devils Claw)

Hoodia gordonii Hypoxis hemerocallidea

Lippia javanica (Musukudu)

Mesembryanthemum tortuosum (kougoed)

Pelargonium sidoides Siphonochilus

aethiopicus (indungulo) Sutherlandia

frutescens Warburgia salutaris (isihaha) and

Xysmalobium undulatum (ishongwe)

B-E vanWyk Journal of Ethnopharmacology 119 (2008) 342ndash355

hellip but which plant to

choose and how to

proceed

Research Methodology

Bio-guided essays

Random Approach

Chemo-taxonomical

Approach

Ethno-botanical

Approach

4

Bio-guided essays

Need to identify the active molecules

bull Biological tests sophisticated

bull Regulatory ndash QC standardization

check for aldulteration

11

Yes

Bio testsIsolation

amp

Purification

Preparative

HPLC

Extracts from various

solvents

Extraction

amp

Fractionation

Bio-essay on

each fraction

Screening

Bioactive NPs

No

Useless fraction

(discarded)

Further

fractionationsIs the fraction

Active

Structure

Elucidation

NMR UV IR CD

Oxydative

degradation

Screening flowchart investigation for bioactive compounds

Classical Research Methodology

6

Challenges

bull Genetic material may have 100rsquos compounds

bull Highly complex

bull Contain artefacts

bull Losses in purification

bull Old methods need large quantities of raw material eg plants

bull Long times to isolate one compound pure determine

structure ndash 6 to 12 months

bull Testingscreening of extracts no longer relevant

Storage

Compounds

7

Most common phrase used in most proposals to fund research based on

Biodiversity and IKS in SA

ldquoDespite having a vast reserve of botanical specimens and a strong indigenous

knowledge system on the medicinal use of these plants South Africa is yet to

launch major registered medicines or drugs based on South African plants into

the local and international biotechnology and pharmaceutical arenardquo

Are we delivering leadsproducts at sufficient rate based on our biodiversity

Possible explanations

bull Emphasis on botanical products difficulties in further development with lack

of regulations

bullNon-Functional interface between Natural products MedChem and Biologists

bullDevelopment cycles in complete ndash lack of co-ordinated and collaborative

research ndash ldquoJohn Wayne syndromerdquo

bullIP ownership

bullLack of assessment of SA chemical diversity ndash fragmented libraries

repositories of samples

bullInability to do high through put purification and structure elucidation of

natural compounds

Further Challenges

bull Academic environment biodiversity samples leave country for research

with limited value addition

bull Fragmented access to local biodiversity

bull No tracking system non coordinated access

bull Local collection not in formats ready for high end and HT

ldquoscreeningtestingrdquo

bull No local ldquoclearing houserdquo to provide trusted collections

bull Government approved and compliance

bull High quality preserved and reproducible

The Challenge in Drug Discovery

Possible Solutions

a) Increase Number of candidate compounds

b) Increase Quality of candidate compounds eg Natural products

Local and International perspectives

Several International InstitutesProgrammes

bull National Cancer Institute (US)

ndash Over 100 000 natural extracts and compounds

ndash Samples collected around the world

ndash Most successful in using these to develop cancer drugs eg taxol vinca

alkaloids

bull South Korea

ndash Govt set up KRIBB

ndash Create natural product libraries

bull Several natural product institutes in China

ndash Repositories of samples

bull Eskitis Institute ndash Australia

bull Novartis - Switzerland

10

Nature Bank

We have a long-term vision for the sustainable use of biodiversity

for the next century and beyond

45000 biota

samples

Plants marine invertebrates from

Australia China PNG

Extracts of biota

Our work with industry has taught us

how to retain only the drug-like

components

200000 Optimised

Nature Bank

fractions

Nature Bank is ready and available for

collaborations with industry academic

groups and PPPs

Fragment Library

Compounds

Scaffold Library

Compound Library

350000 pure compounds

200000 natural product fractions

Cherry-picking

Automated formatting into microtitre plates

Example

Eskitis Institute

bull Own collections

bull Deposited

collections eg

Univ Councils

Other Australia

Univ deposits

100k samples

Formatting and

dispatch

Univ requests

screening of 50k

of their samples

with Pharma

Pharma receives

samples

bull Eskitis weighs and

prepares samples

bull Dispatches

bull Govt is lsquonotifiedrdquo

Local and

International

requests

Our TargetsCreation of a diverse library of natural extracts fractions and chemical

compounds endowed with biological activity and to be used research

programs in a sustainable manner

Extracts

bull Generation of hundreds of

thousands of fractions

bull Structure elucidation of pure

compounds

bull Database for fractions and

compounds

bull Purity storage and format

compatible with HTS

operations

HT

separation

bull Plants

bull Micro-organisms

bull Marine

National Strategy and TargetCreation of a diverse library of natural samples and chemical compounds

endowed with biological activity to be used in research programs in a

sustainable manner

Storage and

Database

Extracts

Plant extract

Clean up

Pre-fractionated extract

Inject

Prep LC

UV

MS

Liquid handler

NMR

DNP AntibaseStructure elucidation taxonomy bioassay data

Information management system

COOH

OO

O

HO

HO

O

O

OH

OH

OH

H3CO

O

O

Chemical Formula C3H3O3bull

Exact Mass 8701

Chemical Formula C25H23O12bull

Exact Mass 51512

Sample Storage

Sample Administration

System

Compounds in vials

Genvac evap

Database

TQD MS

The nuts and bolts

Leveraging the Library ndashConservation

bull Trusted collection

ndash No need to recollect samples

ndash Legal controlled access to industry acedemia

ndash Link to IK databases (NIKMAS)

ndash Link to plant distribution maps

ndash One ldquoshop stoprdquo to the world eg pharma

ndash Control of samples leaving the country

ndash Tool for issuing notifications and permits

bull HCD

ndash New skills training for post graduates

bull Food and cosmetics

ndash Growing market for natural ingredients

1717

Possible Model for the Market

bank

National Repository of Biodiversity samples and

Natural Compounds

bull Legal entity

bull Hosted or independent

bull Government control and access

bull Compound production and storage

bull Core Staff

bull Students

Access

Ownership

Science

Councils

Communities

NGOsUniversities

Deposit

samples

Leveraging the Library ndash Health needs

bull Burden of disease in SA

ndash HIV

ndash TB

ndash Cancer

ndash Cardiovascular disease

ndash Diabetes

ndash Malaria

ndash Alzheimerrsquos

bull Life style diseases

ndash Obesity

bull Food and cosmetics

ndash Growing market for natural ingredients

18

Leveraging the Library Socio-economic

bull Local ldquoclearing houserdquo to provide trusted collections

ndash Government approved and compliance

ndash High quality preserved and reproducible

ndash Controlled access

bull Conservation

ndash No need for huge plants collections

bull Agro-processing

ndash Cultivation and processing through local communities

bull IP creation owned by South Africans

ndash Chemical composition

bull Human Capital Development - skills

bull Economic benefits

ndash Commercialization through Licensing

ndash Local Manufacturing

ndash Access fees19

Thank you

Discussion

21

Structure determination of

molecules

bull NMR

bull MS

bull UV IRCD

copy CSIR 2008 wwwcsircozacopy CSIR 2008 wwwcsircoza

HPLC

pumpHPLC column

INJECTION

- Extract

- Fraction

- Mixture

LCMS

INTERFACE

Splitting dependent

of the LCMS

interfaces used

waste

UV

MS

UV

MS

spectra

1

Speed vac -

off-line or on-line

biological assays

2- LCmicro fractionation

Active fractionsemi

pure compounds

Speed vac -

Storage

Structural

information

Separation by HPLCUVMS

Page 3: Creation of a National Compound Library/Biodiversity ... · Creation of a National Compound Library/Biodiversity Market Bank ... knowledge system on the medicinal use of these plants,

3

South African plants of

commercial interest

Agathosma betulina (Buchu) Aloe ferox

Artemisia afra (Umhlonyane) Aspalathus

linearis (Rooibos tea) Cyclopia genistoides

Harpagophytum procumbens (Devils Claw)

Hoodia gordonii Hypoxis hemerocallidea

Lippia javanica (Musukudu)

Mesembryanthemum tortuosum (kougoed)

Pelargonium sidoides Siphonochilus

aethiopicus (indungulo) Sutherlandia

frutescens Warburgia salutaris (isihaha) and

Xysmalobium undulatum (ishongwe)

B-E vanWyk Journal of Ethnopharmacology 119 (2008) 342ndash355

hellip but which plant to

choose and how to

proceed

Research Methodology

Bio-guided essays

Random Approach

Chemo-taxonomical

Approach

Ethno-botanical

Approach

4

Bio-guided essays

Need to identify the active molecules

bull Biological tests sophisticated

bull Regulatory ndash QC standardization

check for aldulteration

11

Yes

Bio testsIsolation

amp

Purification

Preparative

HPLC

Extracts from various

solvents

Extraction

amp

Fractionation

Bio-essay on

each fraction

Screening

Bioactive NPs

No

Useless fraction

(discarded)

Further

fractionationsIs the fraction

Active

Structure

Elucidation

NMR UV IR CD

Oxydative

degradation

Screening flowchart investigation for bioactive compounds

Classical Research Methodology

6

Challenges

bull Genetic material may have 100rsquos compounds

bull Highly complex

bull Contain artefacts

bull Losses in purification

bull Old methods need large quantities of raw material eg plants

bull Long times to isolate one compound pure determine

structure ndash 6 to 12 months

bull Testingscreening of extracts no longer relevant

Storage

Compounds

7

Most common phrase used in most proposals to fund research based on

Biodiversity and IKS in SA

ldquoDespite having a vast reserve of botanical specimens and a strong indigenous

knowledge system on the medicinal use of these plants South Africa is yet to

launch major registered medicines or drugs based on South African plants into

the local and international biotechnology and pharmaceutical arenardquo

Are we delivering leadsproducts at sufficient rate based on our biodiversity

Possible explanations

bull Emphasis on botanical products difficulties in further development with lack

of regulations

bullNon-Functional interface between Natural products MedChem and Biologists

bullDevelopment cycles in complete ndash lack of co-ordinated and collaborative

research ndash ldquoJohn Wayne syndromerdquo

bullIP ownership

bullLack of assessment of SA chemical diversity ndash fragmented libraries

repositories of samples

bullInability to do high through put purification and structure elucidation of

natural compounds

Further Challenges

bull Academic environment biodiversity samples leave country for research

with limited value addition

bull Fragmented access to local biodiversity

bull No tracking system non coordinated access

bull Local collection not in formats ready for high end and HT

ldquoscreeningtestingrdquo

bull No local ldquoclearing houserdquo to provide trusted collections

bull Government approved and compliance

bull High quality preserved and reproducible

The Challenge in Drug Discovery

Possible Solutions

a) Increase Number of candidate compounds

b) Increase Quality of candidate compounds eg Natural products

Local and International perspectives

Several International InstitutesProgrammes

bull National Cancer Institute (US)

ndash Over 100 000 natural extracts and compounds

ndash Samples collected around the world

ndash Most successful in using these to develop cancer drugs eg taxol vinca

alkaloids

bull South Korea

ndash Govt set up KRIBB

ndash Create natural product libraries

bull Several natural product institutes in China

ndash Repositories of samples

bull Eskitis Institute ndash Australia

bull Novartis - Switzerland

10

Nature Bank

We have a long-term vision for the sustainable use of biodiversity

for the next century and beyond

45000 biota

samples

Plants marine invertebrates from

Australia China PNG

Extracts of biota

Our work with industry has taught us

how to retain only the drug-like

components

200000 Optimised

Nature Bank

fractions

Nature Bank is ready and available for

collaborations with industry academic

groups and PPPs

Fragment Library

Compounds

Scaffold Library

Compound Library

350000 pure compounds

200000 natural product fractions

Cherry-picking

Automated formatting into microtitre plates

Example

Eskitis Institute

bull Own collections

bull Deposited

collections eg

Univ Councils

Other Australia

Univ deposits

100k samples

Formatting and

dispatch

Univ requests

screening of 50k

of their samples

with Pharma

Pharma receives

samples

bull Eskitis weighs and

prepares samples

bull Dispatches

bull Govt is lsquonotifiedrdquo

Local and

International

requests

Our TargetsCreation of a diverse library of natural extracts fractions and chemical

compounds endowed with biological activity and to be used research

programs in a sustainable manner

Extracts

bull Generation of hundreds of

thousands of fractions

bull Structure elucidation of pure

compounds

bull Database for fractions and

compounds

bull Purity storage and format

compatible with HTS

operations

HT

separation

bull Plants

bull Micro-organisms

bull Marine

National Strategy and TargetCreation of a diverse library of natural samples and chemical compounds

endowed with biological activity to be used in research programs in a

sustainable manner

Storage and

Database

Extracts

Plant extract

Clean up

Pre-fractionated extract

Inject

Prep LC

UV

MS

Liquid handler

NMR

DNP AntibaseStructure elucidation taxonomy bioassay data

Information management system

COOH

OO

O

HO

HO

O

O

OH

OH

OH

H3CO

O

O

Chemical Formula C3H3O3bull

Exact Mass 8701

Chemical Formula C25H23O12bull

Exact Mass 51512

Sample Storage

Sample Administration

System

Compounds in vials

Genvac evap

Database

TQD MS

The nuts and bolts

Leveraging the Library ndashConservation

bull Trusted collection

ndash No need to recollect samples

ndash Legal controlled access to industry acedemia

ndash Link to IK databases (NIKMAS)

ndash Link to plant distribution maps

ndash One ldquoshop stoprdquo to the world eg pharma

ndash Control of samples leaving the country

ndash Tool for issuing notifications and permits

bull HCD

ndash New skills training for post graduates

bull Food and cosmetics

ndash Growing market for natural ingredients

1717

Possible Model for the Market

bank

National Repository of Biodiversity samples and

Natural Compounds

bull Legal entity

bull Hosted or independent

bull Government control and access

bull Compound production and storage

bull Core Staff

bull Students

Access

Ownership

Science

Councils

Communities

NGOsUniversities

Deposit

samples

Leveraging the Library ndash Health needs

bull Burden of disease in SA

ndash HIV

ndash TB

ndash Cancer

ndash Cardiovascular disease

ndash Diabetes

ndash Malaria

ndash Alzheimerrsquos

bull Life style diseases

ndash Obesity

bull Food and cosmetics

ndash Growing market for natural ingredients

18

Leveraging the Library Socio-economic

bull Local ldquoclearing houserdquo to provide trusted collections

ndash Government approved and compliance

ndash High quality preserved and reproducible

ndash Controlled access

bull Conservation

ndash No need for huge plants collections

bull Agro-processing

ndash Cultivation and processing through local communities

bull IP creation owned by South Africans

ndash Chemical composition

bull Human Capital Development - skills

bull Economic benefits

ndash Commercialization through Licensing

ndash Local Manufacturing

ndash Access fees19

Thank you

Discussion

21

Structure determination of

molecules

bull NMR

bull MS

bull UV IRCD

copy CSIR 2008 wwwcsircozacopy CSIR 2008 wwwcsircoza

HPLC

pumpHPLC column

INJECTION

- Extract

- Fraction

- Mixture

LCMS

INTERFACE

Splitting dependent

of the LCMS

interfaces used

waste

UV

MS

UV

MS

spectra

1

Speed vac -

off-line or on-line

biological assays

2- LCmicro fractionation

Active fractionsemi

pure compounds

Speed vac -

Storage

Structural

information

Separation by HPLCUVMS

Page 4: Creation of a National Compound Library/Biodiversity ... · Creation of a National Compound Library/Biodiversity Market Bank ... knowledge system on the medicinal use of these plants,

hellip but which plant to

choose and how to

proceed

Research Methodology

Bio-guided essays

Random Approach

Chemo-taxonomical

Approach

Ethno-botanical

Approach

4

Bio-guided essays

Need to identify the active molecules

bull Biological tests sophisticated

bull Regulatory ndash QC standardization

check for aldulteration

11

Yes

Bio testsIsolation

amp

Purification

Preparative

HPLC

Extracts from various

solvents

Extraction

amp

Fractionation

Bio-essay on

each fraction

Screening

Bioactive NPs

No

Useless fraction

(discarded)

Further

fractionationsIs the fraction

Active

Structure

Elucidation

NMR UV IR CD

Oxydative

degradation

Screening flowchart investigation for bioactive compounds

Classical Research Methodology

6

Challenges

bull Genetic material may have 100rsquos compounds

bull Highly complex

bull Contain artefacts

bull Losses in purification

bull Old methods need large quantities of raw material eg plants

bull Long times to isolate one compound pure determine

structure ndash 6 to 12 months

bull Testingscreening of extracts no longer relevant

Storage

Compounds

7

Most common phrase used in most proposals to fund research based on

Biodiversity and IKS in SA

ldquoDespite having a vast reserve of botanical specimens and a strong indigenous

knowledge system on the medicinal use of these plants South Africa is yet to

launch major registered medicines or drugs based on South African plants into

the local and international biotechnology and pharmaceutical arenardquo

Are we delivering leadsproducts at sufficient rate based on our biodiversity

Possible explanations

bull Emphasis on botanical products difficulties in further development with lack

of regulations

bullNon-Functional interface between Natural products MedChem and Biologists

bullDevelopment cycles in complete ndash lack of co-ordinated and collaborative

research ndash ldquoJohn Wayne syndromerdquo

bullIP ownership

bullLack of assessment of SA chemical diversity ndash fragmented libraries

repositories of samples

bullInability to do high through put purification and structure elucidation of

natural compounds

Further Challenges

bull Academic environment biodiversity samples leave country for research

with limited value addition

bull Fragmented access to local biodiversity

bull No tracking system non coordinated access

bull Local collection not in formats ready for high end and HT

ldquoscreeningtestingrdquo

bull No local ldquoclearing houserdquo to provide trusted collections

bull Government approved and compliance

bull High quality preserved and reproducible

The Challenge in Drug Discovery

Possible Solutions

a) Increase Number of candidate compounds

b) Increase Quality of candidate compounds eg Natural products

Local and International perspectives

Several International InstitutesProgrammes

bull National Cancer Institute (US)

ndash Over 100 000 natural extracts and compounds

ndash Samples collected around the world

ndash Most successful in using these to develop cancer drugs eg taxol vinca

alkaloids

bull South Korea

ndash Govt set up KRIBB

ndash Create natural product libraries

bull Several natural product institutes in China

ndash Repositories of samples

bull Eskitis Institute ndash Australia

bull Novartis - Switzerland

10

Nature Bank

We have a long-term vision for the sustainable use of biodiversity

for the next century and beyond

45000 biota

samples

Plants marine invertebrates from

Australia China PNG

Extracts of biota

Our work with industry has taught us

how to retain only the drug-like

components

200000 Optimised

Nature Bank

fractions

Nature Bank is ready and available for

collaborations with industry academic

groups and PPPs

Fragment Library

Compounds

Scaffold Library

Compound Library

350000 pure compounds

200000 natural product fractions

Cherry-picking

Automated formatting into microtitre plates

Example

Eskitis Institute

bull Own collections

bull Deposited

collections eg

Univ Councils

Other Australia

Univ deposits

100k samples

Formatting and

dispatch

Univ requests

screening of 50k

of their samples

with Pharma

Pharma receives

samples

bull Eskitis weighs and

prepares samples

bull Dispatches

bull Govt is lsquonotifiedrdquo

Local and

International

requests

Our TargetsCreation of a diverse library of natural extracts fractions and chemical

compounds endowed with biological activity and to be used research

programs in a sustainable manner

Extracts

bull Generation of hundreds of

thousands of fractions

bull Structure elucidation of pure

compounds

bull Database for fractions and

compounds

bull Purity storage and format

compatible with HTS

operations

HT

separation

bull Plants

bull Micro-organisms

bull Marine

National Strategy and TargetCreation of a diverse library of natural samples and chemical compounds

endowed with biological activity to be used in research programs in a

sustainable manner

Storage and

Database

Extracts

Plant extract

Clean up

Pre-fractionated extract

Inject

Prep LC

UV

MS

Liquid handler

NMR

DNP AntibaseStructure elucidation taxonomy bioassay data

Information management system

COOH

OO

O

HO

HO

O

O

OH

OH

OH

H3CO

O

O

Chemical Formula C3H3O3bull

Exact Mass 8701

Chemical Formula C25H23O12bull

Exact Mass 51512

Sample Storage

Sample Administration

System

Compounds in vials

Genvac evap

Database

TQD MS

The nuts and bolts

Leveraging the Library ndashConservation

bull Trusted collection

ndash No need to recollect samples

ndash Legal controlled access to industry acedemia

ndash Link to IK databases (NIKMAS)

ndash Link to plant distribution maps

ndash One ldquoshop stoprdquo to the world eg pharma

ndash Control of samples leaving the country

ndash Tool for issuing notifications and permits

bull HCD

ndash New skills training for post graduates

bull Food and cosmetics

ndash Growing market for natural ingredients

1717

Possible Model for the Market

bank

National Repository of Biodiversity samples and

Natural Compounds

bull Legal entity

bull Hosted or independent

bull Government control and access

bull Compound production and storage

bull Core Staff

bull Students

Access

Ownership

Science

Councils

Communities

NGOsUniversities

Deposit

samples

Leveraging the Library ndash Health needs

bull Burden of disease in SA

ndash HIV

ndash TB

ndash Cancer

ndash Cardiovascular disease

ndash Diabetes

ndash Malaria

ndash Alzheimerrsquos

bull Life style diseases

ndash Obesity

bull Food and cosmetics

ndash Growing market for natural ingredients

18

Leveraging the Library Socio-economic

bull Local ldquoclearing houserdquo to provide trusted collections

ndash Government approved and compliance

ndash High quality preserved and reproducible

ndash Controlled access

bull Conservation

ndash No need for huge plants collections

bull Agro-processing

ndash Cultivation and processing through local communities

bull IP creation owned by South Africans

ndash Chemical composition

bull Human Capital Development - skills

bull Economic benefits

ndash Commercialization through Licensing

ndash Local Manufacturing

ndash Access fees19

Thank you

Discussion

21

Structure determination of

molecules

bull NMR

bull MS

bull UV IRCD

copy CSIR 2008 wwwcsircozacopy CSIR 2008 wwwcsircoza

HPLC

pumpHPLC column

INJECTION

- Extract

- Fraction

- Mixture

LCMS

INTERFACE

Splitting dependent

of the LCMS

interfaces used

waste

UV

MS

UV

MS

spectra

1

Speed vac -

off-line or on-line

biological assays

2- LCmicro fractionation

Active fractionsemi

pure compounds

Speed vac -

Storage

Structural

information

Separation by HPLCUVMS

Page 5: Creation of a National Compound Library/Biodiversity ... · Creation of a National Compound Library/Biodiversity Market Bank ... knowledge system on the medicinal use of these plants,

11

Yes

Bio testsIsolation

amp

Purification

Preparative

HPLC

Extracts from various

solvents

Extraction

amp

Fractionation

Bio-essay on

each fraction

Screening

Bioactive NPs

No

Useless fraction

(discarded)

Further

fractionationsIs the fraction

Active

Structure

Elucidation

NMR UV IR CD

Oxydative

degradation

Screening flowchart investigation for bioactive compounds

Classical Research Methodology

6

Challenges

bull Genetic material may have 100rsquos compounds

bull Highly complex

bull Contain artefacts

bull Losses in purification

bull Old methods need large quantities of raw material eg plants

bull Long times to isolate one compound pure determine

structure ndash 6 to 12 months

bull Testingscreening of extracts no longer relevant

Storage

Compounds

7

Most common phrase used in most proposals to fund research based on

Biodiversity and IKS in SA

ldquoDespite having a vast reserve of botanical specimens and a strong indigenous

knowledge system on the medicinal use of these plants South Africa is yet to

launch major registered medicines or drugs based on South African plants into

the local and international biotechnology and pharmaceutical arenardquo

Are we delivering leadsproducts at sufficient rate based on our biodiversity

Possible explanations

bull Emphasis on botanical products difficulties in further development with lack

of regulations

bullNon-Functional interface between Natural products MedChem and Biologists

bullDevelopment cycles in complete ndash lack of co-ordinated and collaborative

research ndash ldquoJohn Wayne syndromerdquo

bullIP ownership

bullLack of assessment of SA chemical diversity ndash fragmented libraries

repositories of samples

bullInability to do high through put purification and structure elucidation of

natural compounds

Further Challenges

bull Academic environment biodiversity samples leave country for research

with limited value addition

bull Fragmented access to local biodiversity

bull No tracking system non coordinated access

bull Local collection not in formats ready for high end and HT

ldquoscreeningtestingrdquo

bull No local ldquoclearing houserdquo to provide trusted collections

bull Government approved and compliance

bull High quality preserved and reproducible

The Challenge in Drug Discovery

Possible Solutions

a) Increase Number of candidate compounds

b) Increase Quality of candidate compounds eg Natural products

Local and International perspectives

Several International InstitutesProgrammes

bull National Cancer Institute (US)

ndash Over 100 000 natural extracts and compounds

ndash Samples collected around the world

ndash Most successful in using these to develop cancer drugs eg taxol vinca

alkaloids

bull South Korea

ndash Govt set up KRIBB

ndash Create natural product libraries

bull Several natural product institutes in China

ndash Repositories of samples

bull Eskitis Institute ndash Australia

bull Novartis - Switzerland

10

Nature Bank

We have a long-term vision for the sustainable use of biodiversity

for the next century and beyond

45000 biota

samples

Plants marine invertebrates from

Australia China PNG

Extracts of biota

Our work with industry has taught us

how to retain only the drug-like

components

200000 Optimised

Nature Bank

fractions

Nature Bank is ready and available for

collaborations with industry academic

groups and PPPs

Fragment Library

Compounds

Scaffold Library

Compound Library

350000 pure compounds

200000 natural product fractions

Cherry-picking

Automated formatting into microtitre plates

Example

Eskitis Institute

bull Own collections

bull Deposited

collections eg

Univ Councils

Other Australia

Univ deposits

100k samples

Formatting and

dispatch

Univ requests

screening of 50k

of their samples

with Pharma

Pharma receives

samples

bull Eskitis weighs and

prepares samples

bull Dispatches

bull Govt is lsquonotifiedrdquo

Local and

International

requests

Our TargetsCreation of a diverse library of natural extracts fractions and chemical

compounds endowed with biological activity and to be used research

programs in a sustainable manner

Extracts

bull Generation of hundreds of

thousands of fractions

bull Structure elucidation of pure

compounds

bull Database for fractions and

compounds

bull Purity storage and format

compatible with HTS

operations

HT

separation

bull Plants

bull Micro-organisms

bull Marine

National Strategy and TargetCreation of a diverse library of natural samples and chemical compounds

endowed with biological activity to be used in research programs in a

sustainable manner

Storage and

Database

Extracts

Plant extract

Clean up

Pre-fractionated extract

Inject

Prep LC

UV

MS

Liquid handler

NMR

DNP AntibaseStructure elucidation taxonomy bioassay data

Information management system

COOH

OO

O

HO

HO

O

O

OH

OH

OH

H3CO

O

O

Chemical Formula C3H3O3bull

Exact Mass 8701

Chemical Formula C25H23O12bull

Exact Mass 51512

Sample Storage

Sample Administration

System

Compounds in vials

Genvac evap

Database

TQD MS

The nuts and bolts

Leveraging the Library ndashConservation

bull Trusted collection

ndash No need to recollect samples

ndash Legal controlled access to industry acedemia

ndash Link to IK databases (NIKMAS)

ndash Link to plant distribution maps

ndash One ldquoshop stoprdquo to the world eg pharma

ndash Control of samples leaving the country

ndash Tool for issuing notifications and permits

bull HCD

ndash New skills training for post graduates

bull Food and cosmetics

ndash Growing market for natural ingredients

1717

Possible Model for the Market

bank

National Repository of Biodiversity samples and

Natural Compounds

bull Legal entity

bull Hosted or independent

bull Government control and access

bull Compound production and storage

bull Core Staff

bull Students

Access

Ownership

Science

Councils

Communities

NGOsUniversities

Deposit

samples

Leveraging the Library ndash Health needs

bull Burden of disease in SA

ndash HIV

ndash TB

ndash Cancer

ndash Cardiovascular disease

ndash Diabetes

ndash Malaria

ndash Alzheimerrsquos

bull Life style diseases

ndash Obesity

bull Food and cosmetics

ndash Growing market for natural ingredients

18

Leveraging the Library Socio-economic

bull Local ldquoclearing houserdquo to provide trusted collections

ndash Government approved and compliance

ndash High quality preserved and reproducible

ndash Controlled access

bull Conservation

ndash No need for huge plants collections

bull Agro-processing

ndash Cultivation and processing through local communities

bull IP creation owned by South Africans

ndash Chemical composition

bull Human Capital Development - skills

bull Economic benefits

ndash Commercialization through Licensing

ndash Local Manufacturing

ndash Access fees19

Thank you

Discussion

21

Structure determination of

molecules

bull NMR

bull MS

bull UV IRCD

copy CSIR 2008 wwwcsircozacopy CSIR 2008 wwwcsircoza

HPLC

pumpHPLC column

INJECTION

- Extract

- Fraction

- Mixture

LCMS

INTERFACE

Splitting dependent

of the LCMS

interfaces used

waste

UV

MS

UV

MS

spectra

1

Speed vac -

off-line or on-line

biological assays

2- LCmicro fractionation

Active fractionsemi

pure compounds

Speed vac -

Storage

Structural

information

Separation by HPLCUVMS

Page 6: Creation of a National Compound Library/Biodiversity ... · Creation of a National Compound Library/Biodiversity Market Bank ... knowledge system on the medicinal use of these plants,

6

Challenges

bull Genetic material may have 100rsquos compounds

bull Highly complex

bull Contain artefacts

bull Losses in purification

bull Old methods need large quantities of raw material eg plants

bull Long times to isolate one compound pure determine

structure ndash 6 to 12 months

bull Testingscreening of extracts no longer relevant

Storage

Compounds

7

Most common phrase used in most proposals to fund research based on

Biodiversity and IKS in SA

ldquoDespite having a vast reserve of botanical specimens and a strong indigenous

knowledge system on the medicinal use of these plants South Africa is yet to

launch major registered medicines or drugs based on South African plants into

the local and international biotechnology and pharmaceutical arenardquo

Are we delivering leadsproducts at sufficient rate based on our biodiversity

Possible explanations

bull Emphasis on botanical products difficulties in further development with lack

of regulations

bullNon-Functional interface between Natural products MedChem and Biologists

bullDevelopment cycles in complete ndash lack of co-ordinated and collaborative

research ndash ldquoJohn Wayne syndromerdquo

bullIP ownership

bullLack of assessment of SA chemical diversity ndash fragmented libraries

repositories of samples

bullInability to do high through put purification and structure elucidation of

natural compounds

Further Challenges

bull Academic environment biodiversity samples leave country for research

with limited value addition

bull Fragmented access to local biodiversity

bull No tracking system non coordinated access

bull Local collection not in formats ready for high end and HT

ldquoscreeningtestingrdquo

bull No local ldquoclearing houserdquo to provide trusted collections

bull Government approved and compliance

bull High quality preserved and reproducible

The Challenge in Drug Discovery

Possible Solutions

a) Increase Number of candidate compounds

b) Increase Quality of candidate compounds eg Natural products

Local and International perspectives

Several International InstitutesProgrammes

bull National Cancer Institute (US)

ndash Over 100 000 natural extracts and compounds

ndash Samples collected around the world

ndash Most successful in using these to develop cancer drugs eg taxol vinca

alkaloids

bull South Korea

ndash Govt set up KRIBB

ndash Create natural product libraries

bull Several natural product institutes in China

ndash Repositories of samples

bull Eskitis Institute ndash Australia

bull Novartis - Switzerland

10

Nature Bank

We have a long-term vision for the sustainable use of biodiversity

for the next century and beyond

45000 biota

samples

Plants marine invertebrates from

Australia China PNG

Extracts of biota

Our work with industry has taught us

how to retain only the drug-like

components

200000 Optimised

Nature Bank

fractions

Nature Bank is ready and available for

collaborations with industry academic

groups and PPPs

Fragment Library

Compounds

Scaffold Library

Compound Library

350000 pure compounds

200000 natural product fractions

Cherry-picking

Automated formatting into microtitre plates

Example

Eskitis Institute

bull Own collections

bull Deposited

collections eg

Univ Councils

Other Australia

Univ deposits

100k samples

Formatting and

dispatch

Univ requests

screening of 50k

of their samples

with Pharma

Pharma receives

samples

bull Eskitis weighs and

prepares samples

bull Dispatches

bull Govt is lsquonotifiedrdquo

Local and

International

requests

Our TargetsCreation of a diverse library of natural extracts fractions and chemical

compounds endowed with biological activity and to be used research

programs in a sustainable manner

Extracts

bull Generation of hundreds of

thousands of fractions

bull Structure elucidation of pure

compounds

bull Database for fractions and

compounds

bull Purity storage and format

compatible with HTS

operations

HT

separation

bull Plants

bull Micro-organisms

bull Marine

National Strategy and TargetCreation of a diverse library of natural samples and chemical compounds

endowed with biological activity to be used in research programs in a

sustainable manner

Storage and

Database

Extracts

Plant extract

Clean up

Pre-fractionated extract

Inject

Prep LC

UV

MS

Liquid handler

NMR

DNP AntibaseStructure elucidation taxonomy bioassay data

Information management system

COOH

OO

O

HO

HO

O

O

OH

OH

OH

H3CO

O

O

Chemical Formula C3H3O3bull

Exact Mass 8701

Chemical Formula C25H23O12bull

Exact Mass 51512

Sample Storage

Sample Administration

System

Compounds in vials

Genvac evap

Database

TQD MS

The nuts and bolts

Leveraging the Library ndashConservation

bull Trusted collection

ndash No need to recollect samples

ndash Legal controlled access to industry acedemia

ndash Link to IK databases (NIKMAS)

ndash Link to plant distribution maps

ndash One ldquoshop stoprdquo to the world eg pharma

ndash Control of samples leaving the country

ndash Tool for issuing notifications and permits

bull HCD

ndash New skills training for post graduates

bull Food and cosmetics

ndash Growing market for natural ingredients

1717

Possible Model for the Market

bank

National Repository of Biodiversity samples and

Natural Compounds

bull Legal entity

bull Hosted or independent

bull Government control and access

bull Compound production and storage

bull Core Staff

bull Students

Access

Ownership

Science

Councils

Communities

NGOsUniversities

Deposit

samples

Leveraging the Library ndash Health needs

bull Burden of disease in SA

ndash HIV

ndash TB

ndash Cancer

ndash Cardiovascular disease

ndash Diabetes

ndash Malaria

ndash Alzheimerrsquos

bull Life style diseases

ndash Obesity

bull Food and cosmetics

ndash Growing market for natural ingredients

18

Leveraging the Library Socio-economic

bull Local ldquoclearing houserdquo to provide trusted collections

ndash Government approved and compliance

ndash High quality preserved and reproducible

ndash Controlled access

bull Conservation

ndash No need for huge plants collections

bull Agro-processing

ndash Cultivation and processing through local communities

bull IP creation owned by South Africans

ndash Chemical composition

bull Human Capital Development - skills

bull Economic benefits

ndash Commercialization through Licensing

ndash Local Manufacturing

ndash Access fees19

Thank you

Discussion

21

Structure determination of

molecules

bull NMR

bull MS

bull UV IRCD

copy CSIR 2008 wwwcsircozacopy CSIR 2008 wwwcsircoza

HPLC

pumpHPLC column

INJECTION

- Extract

- Fraction

- Mixture

LCMS

INTERFACE

Splitting dependent

of the LCMS

interfaces used

waste

UV

MS

UV

MS

spectra

1

Speed vac -

off-line or on-line

biological assays

2- LCmicro fractionation

Active fractionsemi

pure compounds

Speed vac -

Storage

Structural

information

Separation by HPLCUVMS

Page 7: Creation of a National Compound Library/Biodiversity ... · Creation of a National Compound Library/Biodiversity Market Bank ... knowledge system on the medicinal use of these plants,

7

Most common phrase used in most proposals to fund research based on

Biodiversity and IKS in SA

ldquoDespite having a vast reserve of botanical specimens and a strong indigenous

knowledge system on the medicinal use of these plants South Africa is yet to

launch major registered medicines or drugs based on South African plants into

the local and international biotechnology and pharmaceutical arenardquo

Are we delivering leadsproducts at sufficient rate based on our biodiversity

Possible explanations

bull Emphasis on botanical products difficulties in further development with lack

of regulations

bullNon-Functional interface between Natural products MedChem and Biologists

bullDevelopment cycles in complete ndash lack of co-ordinated and collaborative

research ndash ldquoJohn Wayne syndromerdquo

bullIP ownership

bullLack of assessment of SA chemical diversity ndash fragmented libraries

repositories of samples

bullInability to do high through put purification and structure elucidation of

natural compounds

Further Challenges

bull Academic environment biodiversity samples leave country for research

with limited value addition

bull Fragmented access to local biodiversity

bull No tracking system non coordinated access

bull Local collection not in formats ready for high end and HT

ldquoscreeningtestingrdquo

bull No local ldquoclearing houserdquo to provide trusted collections

bull Government approved and compliance

bull High quality preserved and reproducible

The Challenge in Drug Discovery

Possible Solutions

a) Increase Number of candidate compounds

b) Increase Quality of candidate compounds eg Natural products

Local and International perspectives

Several International InstitutesProgrammes

bull National Cancer Institute (US)

ndash Over 100 000 natural extracts and compounds

ndash Samples collected around the world

ndash Most successful in using these to develop cancer drugs eg taxol vinca

alkaloids

bull South Korea

ndash Govt set up KRIBB

ndash Create natural product libraries

bull Several natural product institutes in China

ndash Repositories of samples

bull Eskitis Institute ndash Australia

bull Novartis - Switzerland

10

Nature Bank

We have a long-term vision for the sustainable use of biodiversity

for the next century and beyond

45000 biota

samples

Plants marine invertebrates from

Australia China PNG

Extracts of biota

Our work with industry has taught us

how to retain only the drug-like

components

200000 Optimised

Nature Bank

fractions

Nature Bank is ready and available for

collaborations with industry academic

groups and PPPs

Fragment Library

Compounds

Scaffold Library

Compound Library

350000 pure compounds

200000 natural product fractions

Cherry-picking

Automated formatting into microtitre plates

Example

Eskitis Institute

bull Own collections

bull Deposited

collections eg

Univ Councils

Other Australia

Univ deposits

100k samples

Formatting and

dispatch

Univ requests

screening of 50k

of their samples

with Pharma

Pharma receives

samples

bull Eskitis weighs and

prepares samples

bull Dispatches

bull Govt is lsquonotifiedrdquo

Local and

International

requests

Our TargetsCreation of a diverse library of natural extracts fractions and chemical

compounds endowed with biological activity and to be used research

programs in a sustainable manner

Extracts

bull Generation of hundreds of

thousands of fractions

bull Structure elucidation of pure

compounds

bull Database for fractions and

compounds

bull Purity storage and format

compatible with HTS

operations

HT

separation

bull Plants

bull Micro-organisms

bull Marine

National Strategy and TargetCreation of a diverse library of natural samples and chemical compounds

endowed with biological activity to be used in research programs in a

sustainable manner

Storage and

Database

Extracts

Plant extract

Clean up

Pre-fractionated extract

Inject

Prep LC

UV

MS

Liquid handler

NMR

DNP AntibaseStructure elucidation taxonomy bioassay data

Information management system

COOH

OO

O

HO

HO

O

O

OH

OH

OH

H3CO

O

O

Chemical Formula C3H3O3bull

Exact Mass 8701

Chemical Formula C25H23O12bull

Exact Mass 51512

Sample Storage

Sample Administration

System

Compounds in vials

Genvac evap

Database

TQD MS

The nuts and bolts

Leveraging the Library ndashConservation

bull Trusted collection

ndash No need to recollect samples

ndash Legal controlled access to industry acedemia

ndash Link to IK databases (NIKMAS)

ndash Link to plant distribution maps

ndash One ldquoshop stoprdquo to the world eg pharma

ndash Control of samples leaving the country

ndash Tool for issuing notifications and permits

bull HCD

ndash New skills training for post graduates

bull Food and cosmetics

ndash Growing market for natural ingredients

1717

Possible Model for the Market

bank

National Repository of Biodiversity samples and

Natural Compounds

bull Legal entity

bull Hosted or independent

bull Government control and access

bull Compound production and storage

bull Core Staff

bull Students

Access

Ownership

Science

Councils

Communities

NGOsUniversities

Deposit

samples

Leveraging the Library ndash Health needs

bull Burden of disease in SA

ndash HIV

ndash TB

ndash Cancer

ndash Cardiovascular disease

ndash Diabetes

ndash Malaria

ndash Alzheimerrsquos

bull Life style diseases

ndash Obesity

bull Food and cosmetics

ndash Growing market for natural ingredients

18

Leveraging the Library Socio-economic

bull Local ldquoclearing houserdquo to provide trusted collections

ndash Government approved and compliance

ndash High quality preserved and reproducible

ndash Controlled access

bull Conservation

ndash No need for huge plants collections

bull Agro-processing

ndash Cultivation and processing through local communities

bull IP creation owned by South Africans

ndash Chemical composition

bull Human Capital Development - skills

bull Economic benefits

ndash Commercialization through Licensing

ndash Local Manufacturing

ndash Access fees19

Thank you

Discussion

21

Structure determination of

molecules

bull NMR

bull MS

bull UV IRCD

copy CSIR 2008 wwwcsircozacopy CSIR 2008 wwwcsircoza

HPLC

pumpHPLC column

INJECTION

- Extract

- Fraction

- Mixture

LCMS

INTERFACE

Splitting dependent

of the LCMS

interfaces used

waste

UV

MS

UV

MS

spectra

1

Speed vac -

off-line or on-line

biological assays

2- LCmicro fractionation

Active fractionsemi

pure compounds

Speed vac -

Storage

Structural

information

Separation by HPLCUVMS

Page 8: Creation of a National Compound Library/Biodiversity ... · Creation of a National Compound Library/Biodiversity Market Bank ... knowledge system on the medicinal use of these plants,

Further Challenges

bull Academic environment biodiversity samples leave country for research

with limited value addition

bull Fragmented access to local biodiversity

bull No tracking system non coordinated access

bull Local collection not in formats ready for high end and HT

ldquoscreeningtestingrdquo

bull No local ldquoclearing houserdquo to provide trusted collections

bull Government approved and compliance

bull High quality preserved and reproducible

The Challenge in Drug Discovery

Possible Solutions

a) Increase Number of candidate compounds

b) Increase Quality of candidate compounds eg Natural products

Local and International perspectives

Several International InstitutesProgrammes

bull National Cancer Institute (US)

ndash Over 100 000 natural extracts and compounds

ndash Samples collected around the world

ndash Most successful in using these to develop cancer drugs eg taxol vinca

alkaloids

bull South Korea

ndash Govt set up KRIBB

ndash Create natural product libraries

bull Several natural product institutes in China

ndash Repositories of samples

bull Eskitis Institute ndash Australia

bull Novartis - Switzerland

10

Nature Bank

We have a long-term vision for the sustainable use of biodiversity

for the next century and beyond

45000 biota

samples

Plants marine invertebrates from

Australia China PNG

Extracts of biota

Our work with industry has taught us

how to retain only the drug-like

components

200000 Optimised

Nature Bank

fractions

Nature Bank is ready and available for

collaborations with industry academic

groups and PPPs

Fragment Library

Compounds

Scaffold Library

Compound Library

350000 pure compounds

200000 natural product fractions

Cherry-picking

Automated formatting into microtitre plates

Example

Eskitis Institute

bull Own collections

bull Deposited

collections eg

Univ Councils

Other Australia

Univ deposits

100k samples

Formatting and

dispatch

Univ requests

screening of 50k

of their samples

with Pharma

Pharma receives

samples

bull Eskitis weighs and

prepares samples

bull Dispatches

bull Govt is lsquonotifiedrdquo

Local and

International

requests

Our TargetsCreation of a diverse library of natural extracts fractions and chemical

compounds endowed with biological activity and to be used research

programs in a sustainable manner

Extracts

bull Generation of hundreds of

thousands of fractions

bull Structure elucidation of pure

compounds

bull Database for fractions and

compounds

bull Purity storage and format

compatible with HTS

operations

HT

separation

bull Plants

bull Micro-organisms

bull Marine

National Strategy and TargetCreation of a diverse library of natural samples and chemical compounds

endowed with biological activity to be used in research programs in a

sustainable manner

Storage and

Database

Extracts

Plant extract

Clean up

Pre-fractionated extract

Inject

Prep LC

UV

MS

Liquid handler

NMR

DNP AntibaseStructure elucidation taxonomy bioassay data

Information management system

COOH

OO

O

HO

HO

O

O

OH

OH

OH

H3CO

O

O

Chemical Formula C3H3O3bull

Exact Mass 8701

Chemical Formula C25H23O12bull

Exact Mass 51512

Sample Storage

Sample Administration

System

Compounds in vials

Genvac evap

Database

TQD MS

The nuts and bolts

Leveraging the Library ndashConservation

bull Trusted collection

ndash No need to recollect samples

ndash Legal controlled access to industry acedemia

ndash Link to IK databases (NIKMAS)

ndash Link to plant distribution maps

ndash One ldquoshop stoprdquo to the world eg pharma

ndash Control of samples leaving the country

ndash Tool for issuing notifications and permits

bull HCD

ndash New skills training for post graduates

bull Food and cosmetics

ndash Growing market for natural ingredients

1717

Possible Model for the Market

bank

National Repository of Biodiversity samples and

Natural Compounds

bull Legal entity

bull Hosted or independent

bull Government control and access

bull Compound production and storage

bull Core Staff

bull Students

Access

Ownership

Science

Councils

Communities

NGOsUniversities

Deposit

samples

Leveraging the Library ndash Health needs

bull Burden of disease in SA

ndash HIV

ndash TB

ndash Cancer

ndash Cardiovascular disease

ndash Diabetes

ndash Malaria

ndash Alzheimerrsquos

bull Life style diseases

ndash Obesity

bull Food and cosmetics

ndash Growing market for natural ingredients

18

Leveraging the Library Socio-economic

bull Local ldquoclearing houserdquo to provide trusted collections

ndash Government approved and compliance

ndash High quality preserved and reproducible

ndash Controlled access

bull Conservation

ndash No need for huge plants collections

bull Agro-processing

ndash Cultivation and processing through local communities

bull IP creation owned by South Africans

ndash Chemical composition

bull Human Capital Development - skills

bull Economic benefits

ndash Commercialization through Licensing

ndash Local Manufacturing

ndash Access fees19

Thank you

Discussion

21

Structure determination of

molecules

bull NMR

bull MS

bull UV IRCD

copy CSIR 2008 wwwcsircozacopy CSIR 2008 wwwcsircoza

HPLC

pumpHPLC column

INJECTION

- Extract

- Fraction

- Mixture

LCMS

INTERFACE

Splitting dependent

of the LCMS

interfaces used

waste

UV

MS

UV

MS

spectra

1

Speed vac -

off-line or on-line

biological assays

2- LCmicro fractionation

Active fractionsemi

pure compounds

Speed vac -

Storage

Structural

information

Separation by HPLCUVMS

Page 9: Creation of a National Compound Library/Biodiversity ... · Creation of a National Compound Library/Biodiversity Market Bank ... knowledge system on the medicinal use of these plants,

The Challenge in Drug Discovery

Possible Solutions

a) Increase Number of candidate compounds

b) Increase Quality of candidate compounds eg Natural products

Local and International perspectives

Several International InstitutesProgrammes

bull National Cancer Institute (US)

ndash Over 100 000 natural extracts and compounds

ndash Samples collected around the world

ndash Most successful in using these to develop cancer drugs eg taxol vinca

alkaloids

bull South Korea

ndash Govt set up KRIBB

ndash Create natural product libraries

bull Several natural product institutes in China

ndash Repositories of samples

bull Eskitis Institute ndash Australia

bull Novartis - Switzerland

10

Nature Bank

We have a long-term vision for the sustainable use of biodiversity

for the next century and beyond

45000 biota

samples

Plants marine invertebrates from

Australia China PNG

Extracts of biota

Our work with industry has taught us

how to retain only the drug-like

components

200000 Optimised

Nature Bank

fractions

Nature Bank is ready and available for

collaborations with industry academic

groups and PPPs

Fragment Library

Compounds

Scaffold Library

Compound Library

350000 pure compounds

200000 natural product fractions

Cherry-picking

Automated formatting into microtitre plates

Example

Eskitis Institute

bull Own collections

bull Deposited

collections eg

Univ Councils

Other Australia

Univ deposits

100k samples

Formatting and

dispatch

Univ requests

screening of 50k

of their samples

with Pharma

Pharma receives

samples

bull Eskitis weighs and

prepares samples

bull Dispatches

bull Govt is lsquonotifiedrdquo

Local and

International

requests

Our TargetsCreation of a diverse library of natural extracts fractions and chemical

compounds endowed with biological activity and to be used research

programs in a sustainable manner

Extracts

bull Generation of hundreds of

thousands of fractions

bull Structure elucidation of pure

compounds

bull Database for fractions and

compounds

bull Purity storage and format

compatible with HTS

operations

HT

separation

bull Plants

bull Micro-organisms

bull Marine

National Strategy and TargetCreation of a diverse library of natural samples and chemical compounds

endowed with biological activity to be used in research programs in a

sustainable manner

Storage and

Database

Extracts

Plant extract

Clean up

Pre-fractionated extract

Inject

Prep LC

UV

MS

Liquid handler

NMR

DNP AntibaseStructure elucidation taxonomy bioassay data

Information management system

COOH

OO

O

HO

HO

O

O

OH

OH

OH

H3CO

O

O

Chemical Formula C3H3O3bull

Exact Mass 8701

Chemical Formula C25H23O12bull

Exact Mass 51512

Sample Storage

Sample Administration

System

Compounds in vials

Genvac evap

Database

TQD MS

The nuts and bolts

Leveraging the Library ndashConservation

bull Trusted collection

ndash No need to recollect samples

ndash Legal controlled access to industry acedemia

ndash Link to IK databases (NIKMAS)

ndash Link to plant distribution maps

ndash One ldquoshop stoprdquo to the world eg pharma

ndash Control of samples leaving the country

ndash Tool for issuing notifications and permits

bull HCD

ndash New skills training for post graduates

bull Food and cosmetics

ndash Growing market for natural ingredients

1717

Possible Model for the Market

bank

National Repository of Biodiversity samples and

Natural Compounds

bull Legal entity

bull Hosted or independent

bull Government control and access

bull Compound production and storage

bull Core Staff

bull Students

Access

Ownership

Science

Councils

Communities

NGOsUniversities

Deposit

samples

Leveraging the Library ndash Health needs

bull Burden of disease in SA

ndash HIV

ndash TB

ndash Cancer

ndash Cardiovascular disease

ndash Diabetes

ndash Malaria

ndash Alzheimerrsquos

bull Life style diseases

ndash Obesity

bull Food and cosmetics

ndash Growing market for natural ingredients

18

Leveraging the Library Socio-economic

bull Local ldquoclearing houserdquo to provide trusted collections

ndash Government approved and compliance

ndash High quality preserved and reproducible

ndash Controlled access

bull Conservation

ndash No need for huge plants collections

bull Agro-processing

ndash Cultivation and processing through local communities

bull IP creation owned by South Africans

ndash Chemical composition

bull Human Capital Development - skills

bull Economic benefits

ndash Commercialization through Licensing

ndash Local Manufacturing

ndash Access fees19

Thank you

Discussion

21

Structure determination of

molecules

bull NMR

bull MS

bull UV IRCD

copy CSIR 2008 wwwcsircozacopy CSIR 2008 wwwcsircoza

HPLC

pumpHPLC column

INJECTION

- Extract

- Fraction

- Mixture

LCMS

INTERFACE

Splitting dependent

of the LCMS

interfaces used

waste

UV

MS

UV

MS

spectra

1

Speed vac -

off-line or on-line

biological assays

2- LCmicro fractionation

Active fractionsemi

pure compounds

Speed vac -

Storage

Structural

information

Separation by HPLCUVMS

Page 10: Creation of a National Compound Library/Biodiversity ... · Creation of a National Compound Library/Biodiversity Market Bank ... knowledge system on the medicinal use of these plants,

Local and International perspectives

Several International InstitutesProgrammes

bull National Cancer Institute (US)

ndash Over 100 000 natural extracts and compounds

ndash Samples collected around the world

ndash Most successful in using these to develop cancer drugs eg taxol vinca

alkaloids

bull South Korea

ndash Govt set up KRIBB

ndash Create natural product libraries

bull Several natural product institutes in China

ndash Repositories of samples

bull Eskitis Institute ndash Australia

bull Novartis - Switzerland

10

Nature Bank

We have a long-term vision for the sustainable use of biodiversity

for the next century and beyond

45000 biota

samples

Plants marine invertebrates from

Australia China PNG

Extracts of biota

Our work with industry has taught us

how to retain only the drug-like

components

200000 Optimised

Nature Bank

fractions

Nature Bank is ready and available for

collaborations with industry academic

groups and PPPs

Fragment Library

Compounds

Scaffold Library

Compound Library

350000 pure compounds

200000 natural product fractions

Cherry-picking

Automated formatting into microtitre plates

Example

Eskitis Institute

bull Own collections

bull Deposited

collections eg

Univ Councils

Other Australia

Univ deposits

100k samples

Formatting and

dispatch

Univ requests

screening of 50k

of their samples

with Pharma

Pharma receives

samples

bull Eskitis weighs and

prepares samples

bull Dispatches

bull Govt is lsquonotifiedrdquo

Local and

International

requests

Our TargetsCreation of a diverse library of natural extracts fractions and chemical

compounds endowed with biological activity and to be used research

programs in a sustainable manner

Extracts

bull Generation of hundreds of

thousands of fractions

bull Structure elucidation of pure

compounds

bull Database for fractions and

compounds

bull Purity storage and format

compatible with HTS

operations

HT

separation

bull Plants

bull Micro-organisms

bull Marine

National Strategy and TargetCreation of a diverse library of natural samples and chemical compounds

endowed with biological activity to be used in research programs in a

sustainable manner

Storage and

Database

Extracts

Plant extract

Clean up

Pre-fractionated extract

Inject

Prep LC

UV

MS

Liquid handler

NMR

DNP AntibaseStructure elucidation taxonomy bioassay data

Information management system

COOH

OO

O

HO

HO

O

O

OH

OH

OH

H3CO

O

O

Chemical Formula C3H3O3bull

Exact Mass 8701

Chemical Formula C25H23O12bull

Exact Mass 51512

Sample Storage

Sample Administration

System

Compounds in vials

Genvac evap

Database

TQD MS

The nuts and bolts

Leveraging the Library ndashConservation

bull Trusted collection

ndash No need to recollect samples

ndash Legal controlled access to industry acedemia

ndash Link to IK databases (NIKMAS)

ndash Link to plant distribution maps

ndash One ldquoshop stoprdquo to the world eg pharma

ndash Control of samples leaving the country

ndash Tool for issuing notifications and permits

bull HCD

ndash New skills training for post graduates

bull Food and cosmetics

ndash Growing market for natural ingredients

1717

Possible Model for the Market

bank

National Repository of Biodiversity samples and

Natural Compounds

bull Legal entity

bull Hosted or independent

bull Government control and access

bull Compound production and storage

bull Core Staff

bull Students

Access

Ownership

Science

Councils

Communities

NGOsUniversities

Deposit

samples

Leveraging the Library ndash Health needs

bull Burden of disease in SA

ndash HIV

ndash TB

ndash Cancer

ndash Cardiovascular disease

ndash Diabetes

ndash Malaria

ndash Alzheimerrsquos

bull Life style diseases

ndash Obesity

bull Food and cosmetics

ndash Growing market for natural ingredients

18

Leveraging the Library Socio-economic

bull Local ldquoclearing houserdquo to provide trusted collections

ndash Government approved and compliance

ndash High quality preserved and reproducible

ndash Controlled access

bull Conservation

ndash No need for huge plants collections

bull Agro-processing

ndash Cultivation and processing through local communities

bull IP creation owned by South Africans

ndash Chemical composition

bull Human Capital Development - skills

bull Economic benefits

ndash Commercialization through Licensing

ndash Local Manufacturing

ndash Access fees19

Thank you

Discussion

21

Structure determination of

molecules

bull NMR

bull MS

bull UV IRCD

copy CSIR 2008 wwwcsircozacopy CSIR 2008 wwwcsircoza

HPLC

pumpHPLC column

INJECTION

- Extract

- Fraction

- Mixture

LCMS

INTERFACE

Splitting dependent

of the LCMS

interfaces used

waste

UV

MS

UV

MS

spectra

1

Speed vac -

off-line or on-line

biological assays

2- LCmicro fractionation

Active fractionsemi

pure compounds

Speed vac -

Storage

Structural

information

Separation by HPLCUVMS

Page 11: Creation of a National Compound Library/Biodiversity ... · Creation of a National Compound Library/Biodiversity Market Bank ... knowledge system on the medicinal use of these plants,

Nature Bank

We have a long-term vision for the sustainable use of biodiversity

for the next century and beyond

45000 biota

samples

Plants marine invertebrates from

Australia China PNG

Extracts of biota

Our work with industry has taught us

how to retain only the drug-like

components

200000 Optimised

Nature Bank

fractions

Nature Bank is ready and available for

collaborations with industry academic

groups and PPPs

Fragment Library

Compounds

Scaffold Library

Compound Library

350000 pure compounds

200000 natural product fractions

Cherry-picking

Automated formatting into microtitre plates

Example

Eskitis Institute

bull Own collections

bull Deposited

collections eg

Univ Councils

Other Australia

Univ deposits

100k samples

Formatting and

dispatch

Univ requests

screening of 50k

of their samples

with Pharma

Pharma receives

samples

bull Eskitis weighs and

prepares samples

bull Dispatches

bull Govt is lsquonotifiedrdquo

Local and

International

requests

Our TargetsCreation of a diverse library of natural extracts fractions and chemical

compounds endowed with biological activity and to be used research

programs in a sustainable manner

Extracts

bull Generation of hundreds of

thousands of fractions

bull Structure elucidation of pure

compounds

bull Database for fractions and

compounds

bull Purity storage and format

compatible with HTS

operations

HT

separation

bull Plants

bull Micro-organisms

bull Marine

National Strategy and TargetCreation of a diverse library of natural samples and chemical compounds

endowed with biological activity to be used in research programs in a

sustainable manner

Storage and

Database

Extracts

Plant extract

Clean up

Pre-fractionated extract

Inject

Prep LC

UV

MS

Liquid handler

NMR

DNP AntibaseStructure elucidation taxonomy bioassay data

Information management system

COOH

OO

O

HO

HO

O

O

OH

OH

OH

H3CO

O

O

Chemical Formula C3H3O3bull

Exact Mass 8701

Chemical Formula C25H23O12bull

Exact Mass 51512

Sample Storage

Sample Administration

System

Compounds in vials

Genvac evap

Database

TQD MS

The nuts and bolts

Leveraging the Library ndashConservation

bull Trusted collection

ndash No need to recollect samples

ndash Legal controlled access to industry acedemia

ndash Link to IK databases (NIKMAS)

ndash Link to plant distribution maps

ndash One ldquoshop stoprdquo to the world eg pharma

ndash Control of samples leaving the country

ndash Tool for issuing notifications and permits

bull HCD

ndash New skills training for post graduates

bull Food and cosmetics

ndash Growing market for natural ingredients

1717

Possible Model for the Market

bank

National Repository of Biodiversity samples and

Natural Compounds

bull Legal entity

bull Hosted or independent

bull Government control and access

bull Compound production and storage

bull Core Staff

bull Students

Access

Ownership

Science

Councils

Communities

NGOsUniversities

Deposit

samples

Leveraging the Library ndash Health needs

bull Burden of disease in SA

ndash HIV

ndash TB

ndash Cancer

ndash Cardiovascular disease

ndash Diabetes

ndash Malaria

ndash Alzheimerrsquos

bull Life style diseases

ndash Obesity

bull Food and cosmetics

ndash Growing market for natural ingredients

18

Leveraging the Library Socio-economic

bull Local ldquoclearing houserdquo to provide trusted collections

ndash Government approved and compliance

ndash High quality preserved and reproducible

ndash Controlled access

bull Conservation

ndash No need for huge plants collections

bull Agro-processing

ndash Cultivation and processing through local communities

bull IP creation owned by South Africans

ndash Chemical composition

bull Human Capital Development - skills

bull Economic benefits

ndash Commercialization through Licensing

ndash Local Manufacturing

ndash Access fees19

Thank you

Discussion

21

Structure determination of

molecules

bull NMR

bull MS

bull UV IRCD

copy CSIR 2008 wwwcsircozacopy CSIR 2008 wwwcsircoza

HPLC

pumpHPLC column

INJECTION

- Extract

- Fraction

- Mixture

LCMS

INTERFACE

Splitting dependent

of the LCMS

interfaces used

waste

UV

MS

UV

MS

spectra

1

Speed vac -

off-line or on-line

biological assays

2- LCmicro fractionation

Active fractionsemi

pure compounds

Speed vac -

Storage

Structural

information

Separation by HPLCUVMS

Page 12: Creation of a National Compound Library/Biodiversity ... · Creation of a National Compound Library/Biodiversity Market Bank ... knowledge system on the medicinal use of these plants,

Compound Library

350000 pure compounds

200000 natural product fractions

Cherry-picking

Automated formatting into microtitre plates

Example

Eskitis Institute

bull Own collections

bull Deposited

collections eg

Univ Councils

Other Australia

Univ deposits

100k samples

Formatting and

dispatch

Univ requests

screening of 50k

of their samples

with Pharma

Pharma receives

samples

bull Eskitis weighs and

prepares samples

bull Dispatches

bull Govt is lsquonotifiedrdquo

Local and

International

requests

Our TargetsCreation of a diverse library of natural extracts fractions and chemical

compounds endowed with biological activity and to be used research

programs in a sustainable manner

Extracts

bull Generation of hundreds of

thousands of fractions

bull Structure elucidation of pure

compounds

bull Database for fractions and

compounds

bull Purity storage and format

compatible with HTS

operations

HT

separation

bull Plants

bull Micro-organisms

bull Marine

National Strategy and TargetCreation of a diverse library of natural samples and chemical compounds

endowed with biological activity to be used in research programs in a

sustainable manner

Storage and

Database

Extracts

Plant extract

Clean up

Pre-fractionated extract

Inject

Prep LC

UV

MS

Liquid handler

NMR

DNP AntibaseStructure elucidation taxonomy bioassay data

Information management system

COOH

OO

O

HO

HO

O

O

OH

OH

OH

H3CO

O

O

Chemical Formula C3H3O3bull

Exact Mass 8701

Chemical Formula C25H23O12bull

Exact Mass 51512

Sample Storage

Sample Administration

System

Compounds in vials

Genvac evap

Database

TQD MS

The nuts and bolts

Leveraging the Library ndashConservation

bull Trusted collection

ndash No need to recollect samples

ndash Legal controlled access to industry acedemia

ndash Link to IK databases (NIKMAS)

ndash Link to plant distribution maps

ndash One ldquoshop stoprdquo to the world eg pharma

ndash Control of samples leaving the country

ndash Tool for issuing notifications and permits

bull HCD

ndash New skills training for post graduates

bull Food and cosmetics

ndash Growing market for natural ingredients

1717

Possible Model for the Market

bank

National Repository of Biodiversity samples and

Natural Compounds

bull Legal entity

bull Hosted or independent

bull Government control and access

bull Compound production and storage

bull Core Staff

bull Students

Access

Ownership

Science

Councils

Communities

NGOsUniversities

Deposit

samples

Leveraging the Library ndash Health needs

bull Burden of disease in SA

ndash HIV

ndash TB

ndash Cancer

ndash Cardiovascular disease

ndash Diabetes

ndash Malaria

ndash Alzheimerrsquos

bull Life style diseases

ndash Obesity

bull Food and cosmetics

ndash Growing market for natural ingredients

18

Leveraging the Library Socio-economic

bull Local ldquoclearing houserdquo to provide trusted collections

ndash Government approved and compliance

ndash High quality preserved and reproducible

ndash Controlled access

bull Conservation

ndash No need for huge plants collections

bull Agro-processing

ndash Cultivation and processing through local communities

bull IP creation owned by South Africans

ndash Chemical composition

bull Human Capital Development - skills

bull Economic benefits

ndash Commercialization through Licensing

ndash Local Manufacturing

ndash Access fees19

Thank you

Discussion

21

Structure determination of

molecules

bull NMR

bull MS

bull UV IRCD

copy CSIR 2008 wwwcsircozacopy CSIR 2008 wwwcsircoza

HPLC

pumpHPLC column

INJECTION

- Extract

- Fraction

- Mixture

LCMS

INTERFACE

Splitting dependent

of the LCMS

interfaces used

waste

UV

MS

UV

MS

spectra

1

Speed vac -

off-line or on-line

biological assays

2- LCmicro fractionation

Active fractionsemi

pure compounds

Speed vac -

Storage

Structural

information

Separation by HPLCUVMS

Page 13: Creation of a National Compound Library/Biodiversity ... · Creation of a National Compound Library/Biodiversity Market Bank ... knowledge system on the medicinal use of these plants,

Example

Eskitis Institute

bull Own collections

bull Deposited

collections eg

Univ Councils

Other Australia

Univ deposits

100k samples

Formatting and

dispatch

Univ requests

screening of 50k

of their samples

with Pharma

Pharma receives

samples

bull Eskitis weighs and

prepares samples

bull Dispatches

bull Govt is lsquonotifiedrdquo

Local and

International

requests

Our TargetsCreation of a diverse library of natural extracts fractions and chemical

compounds endowed with biological activity and to be used research

programs in a sustainable manner

Extracts

bull Generation of hundreds of

thousands of fractions

bull Structure elucidation of pure

compounds

bull Database for fractions and

compounds

bull Purity storage and format

compatible with HTS

operations

HT

separation

bull Plants

bull Micro-organisms

bull Marine

National Strategy and TargetCreation of a diverse library of natural samples and chemical compounds

endowed with biological activity to be used in research programs in a

sustainable manner

Storage and

Database

Extracts

Plant extract

Clean up

Pre-fractionated extract

Inject

Prep LC

UV

MS

Liquid handler

NMR

DNP AntibaseStructure elucidation taxonomy bioassay data

Information management system

COOH

OO

O

HO

HO

O

O

OH

OH

OH

H3CO

O

O

Chemical Formula C3H3O3bull

Exact Mass 8701

Chemical Formula C25H23O12bull

Exact Mass 51512

Sample Storage

Sample Administration

System

Compounds in vials

Genvac evap

Database

TQD MS

The nuts and bolts

Leveraging the Library ndashConservation

bull Trusted collection

ndash No need to recollect samples

ndash Legal controlled access to industry acedemia

ndash Link to IK databases (NIKMAS)

ndash Link to plant distribution maps

ndash One ldquoshop stoprdquo to the world eg pharma

ndash Control of samples leaving the country

ndash Tool for issuing notifications and permits

bull HCD

ndash New skills training for post graduates

bull Food and cosmetics

ndash Growing market for natural ingredients

1717

Possible Model for the Market

bank

National Repository of Biodiversity samples and

Natural Compounds

bull Legal entity

bull Hosted or independent

bull Government control and access

bull Compound production and storage

bull Core Staff

bull Students

Access

Ownership

Science

Councils

Communities

NGOsUniversities

Deposit

samples

Leveraging the Library ndash Health needs

bull Burden of disease in SA

ndash HIV

ndash TB

ndash Cancer

ndash Cardiovascular disease

ndash Diabetes

ndash Malaria

ndash Alzheimerrsquos

bull Life style diseases

ndash Obesity

bull Food and cosmetics

ndash Growing market for natural ingredients

18

Leveraging the Library Socio-economic

bull Local ldquoclearing houserdquo to provide trusted collections

ndash Government approved and compliance

ndash High quality preserved and reproducible

ndash Controlled access

bull Conservation

ndash No need for huge plants collections

bull Agro-processing

ndash Cultivation and processing through local communities

bull IP creation owned by South Africans

ndash Chemical composition

bull Human Capital Development - skills

bull Economic benefits

ndash Commercialization through Licensing

ndash Local Manufacturing

ndash Access fees19

Thank you

Discussion

21

Structure determination of

molecules

bull NMR

bull MS

bull UV IRCD

copy CSIR 2008 wwwcsircozacopy CSIR 2008 wwwcsircoza

HPLC

pumpHPLC column

INJECTION

- Extract

- Fraction

- Mixture

LCMS

INTERFACE

Splitting dependent

of the LCMS

interfaces used

waste

UV

MS

UV

MS

spectra

1

Speed vac -

off-line or on-line

biological assays

2- LCmicro fractionation

Active fractionsemi

pure compounds

Speed vac -

Storage

Structural

information

Separation by HPLCUVMS

Page 14: Creation of a National Compound Library/Biodiversity ... · Creation of a National Compound Library/Biodiversity Market Bank ... knowledge system on the medicinal use of these plants,

Our TargetsCreation of a diverse library of natural extracts fractions and chemical

compounds endowed with biological activity and to be used research

programs in a sustainable manner

Extracts

bull Generation of hundreds of

thousands of fractions

bull Structure elucidation of pure

compounds

bull Database for fractions and

compounds

bull Purity storage and format

compatible with HTS

operations

HT

separation

bull Plants

bull Micro-organisms

bull Marine

National Strategy and TargetCreation of a diverse library of natural samples and chemical compounds

endowed with biological activity to be used in research programs in a

sustainable manner

Storage and

Database

Extracts

Plant extract

Clean up

Pre-fractionated extract

Inject

Prep LC

UV

MS

Liquid handler

NMR

DNP AntibaseStructure elucidation taxonomy bioassay data

Information management system

COOH

OO

O

HO

HO

O

O

OH

OH

OH

H3CO

O

O

Chemical Formula C3H3O3bull

Exact Mass 8701

Chemical Formula C25H23O12bull

Exact Mass 51512

Sample Storage

Sample Administration

System

Compounds in vials

Genvac evap

Database

TQD MS

The nuts and bolts

Leveraging the Library ndashConservation

bull Trusted collection

ndash No need to recollect samples

ndash Legal controlled access to industry acedemia

ndash Link to IK databases (NIKMAS)

ndash Link to plant distribution maps

ndash One ldquoshop stoprdquo to the world eg pharma

ndash Control of samples leaving the country

ndash Tool for issuing notifications and permits

bull HCD

ndash New skills training for post graduates

bull Food and cosmetics

ndash Growing market for natural ingredients

1717

Possible Model for the Market

bank

National Repository of Biodiversity samples and

Natural Compounds

bull Legal entity

bull Hosted or independent

bull Government control and access

bull Compound production and storage

bull Core Staff

bull Students

Access

Ownership

Science

Councils

Communities

NGOsUniversities

Deposit

samples

Leveraging the Library ndash Health needs

bull Burden of disease in SA

ndash HIV

ndash TB

ndash Cancer

ndash Cardiovascular disease

ndash Diabetes

ndash Malaria

ndash Alzheimerrsquos

bull Life style diseases

ndash Obesity

bull Food and cosmetics

ndash Growing market for natural ingredients

18

Leveraging the Library Socio-economic

bull Local ldquoclearing houserdquo to provide trusted collections

ndash Government approved and compliance

ndash High quality preserved and reproducible

ndash Controlled access

bull Conservation

ndash No need for huge plants collections

bull Agro-processing

ndash Cultivation and processing through local communities

bull IP creation owned by South Africans

ndash Chemical composition

bull Human Capital Development - skills

bull Economic benefits

ndash Commercialization through Licensing

ndash Local Manufacturing

ndash Access fees19

Thank you

Discussion

21

Structure determination of

molecules

bull NMR

bull MS

bull UV IRCD

copy CSIR 2008 wwwcsircozacopy CSIR 2008 wwwcsircoza

HPLC

pumpHPLC column

INJECTION

- Extract

- Fraction

- Mixture

LCMS

INTERFACE

Splitting dependent

of the LCMS

interfaces used

waste

UV

MS

UV

MS

spectra

1

Speed vac -

off-line or on-line

biological assays

2- LCmicro fractionation

Active fractionsemi

pure compounds

Speed vac -

Storage

Structural

information

Separation by HPLCUVMS

Page 15: Creation of a National Compound Library/Biodiversity ... · Creation of a National Compound Library/Biodiversity Market Bank ... knowledge system on the medicinal use of these plants,

National Strategy and TargetCreation of a diverse library of natural samples and chemical compounds

endowed with biological activity to be used in research programs in a

sustainable manner

Storage and

Database

Extracts

Plant extract

Clean up

Pre-fractionated extract

Inject

Prep LC

UV

MS

Liquid handler

NMR

DNP AntibaseStructure elucidation taxonomy bioassay data

Information management system

COOH

OO

O

HO

HO

O

O

OH

OH

OH

H3CO

O

O

Chemical Formula C3H3O3bull

Exact Mass 8701

Chemical Formula C25H23O12bull

Exact Mass 51512

Sample Storage

Sample Administration

System

Compounds in vials

Genvac evap

Database

TQD MS

The nuts and bolts

Leveraging the Library ndashConservation

bull Trusted collection

ndash No need to recollect samples

ndash Legal controlled access to industry acedemia

ndash Link to IK databases (NIKMAS)

ndash Link to plant distribution maps

ndash One ldquoshop stoprdquo to the world eg pharma

ndash Control of samples leaving the country

ndash Tool for issuing notifications and permits

bull HCD

ndash New skills training for post graduates

bull Food and cosmetics

ndash Growing market for natural ingredients

1717

Possible Model for the Market

bank

National Repository of Biodiversity samples and

Natural Compounds

bull Legal entity

bull Hosted or independent

bull Government control and access

bull Compound production and storage

bull Core Staff

bull Students

Access

Ownership

Science

Councils

Communities

NGOsUniversities

Deposit

samples

Leveraging the Library ndash Health needs

bull Burden of disease in SA

ndash HIV

ndash TB

ndash Cancer

ndash Cardiovascular disease

ndash Diabetes

ndash Malaria

ndash Alzheimerrsquos

bull Life style diseases

ndash Obesity

bull Food and cosmetics

ndash Growing market for natural ingredients

18

Leveraging the Library Socio-economic

bull Local ldquoclearing houserdquo to provide trusted collections

ndash Government approved and compliance

ndash High quality preserved and reproducible

ndash Controlled access

bull Conservation

ndash No need for huge plants collections

bull Agro-processing

ndash Cultivation and processing through local communities

bull IP creation owned by South Africans

ndash Chemical composition

bull Human Capital Development - skills

bull Economic benefits

ndash Commercialization through Licensing

ndash Local Manufacturing

ndash Access fees19

Thank you

Discussion

21

Structure determination of

molecules

bull NMR

bull MS

bull UV IRCD

copy CSIR 2008 wwwcsircozacopy CSIR 2008 wwwcsircoza

HPLC

pumpHPLC column

INJECTION

- Extract

- Fraction

- Mixture

LCMS

INTERFACE

Splitting dependent

of the LCMS

interfaces used

waste

UV

MS

UV

MS

spectra

1

Speed vac -

off-line or on-line

biological assays

2- LCmicro fractionation

Active fractionsemi

pure compounds

Speed vac -

Storage

Structural

information

Separation by HPLCUVMS

Page 16: Creation of a National Compound Library/Biodiversity ... · Creation of a National Compound Library/Biodiversity Market Bank ... knowledge system on the medicinal use of these plants,

Plant extract

Clean up

Pre-fractionated extract

Inject

Prep LC

UV

MS

Liquid handler

NMR

DNP AntibaseStructure elucidation taxonomy bioassay data

Information management system

COOH

OO

O

HO

HO

O

O

OH

OH

OH

H3CO

O

O

Chemical Formula C3H3O3bull

Exact Mass 8701

Chemical Formula C25H23O12bull

Exact Mass 51512

Sample Storage

Sample Administration

System

Compounds in vials

Genvac evap

Database

TQD MS

The nuts and bolts

Leveraging the Library ndashConservation

bull Trusted collection

ndash No need to recollect samples

ndash Legal controlled access to industry acedemia

ndash Link to IK databases (NIKMAS)

ndash Link to plant distribution maps

ndash One ldquoshop stoprdquo to the world eg pharma

ndash Control of samples leaving the country

ndash Tool for issuing notifications and permits

bull HCD

ndash New skills training for post graduates

bull Food and cosmetics

ndash Growing market for natural ingredients

1717

Possible Model for the Market

bank

National Repository of Biodiversity samples and

Natural Compounds

bull Legal entity

bull Hosted or independent

bull Government control and access

bull Compound production and storage

bull Core Staff

bull Students

Access

Ownership

Science

Councils

Communities

NGOsUniversities

Deposit

samples

Leveraging the Library ndash Health needs

bull Burden of disease in SA

ndash HIV

ndash TB

ndash Cancer

ndash Cardiovascular disease

ndash Diabetes

ndash Malaria

ndash Alzheimerrsquos

bull Life style diseases

ndash Obesity

bull Food and cosmetics

ndash Growing market for natural ingredients

18

Leveraging the Library Socio-economic

bull Local ldquoclearing houserdquo to provide trusted collections

ndash Government approved and compliance

ndash High quality preserved and reproducible

ndash Controlled access

bull Conservation

ndash No need for huge plants collections

bull Agro-processing

ndash Cultivation and processing through local communities

bull IP creation owned by South Africans

ndash Chemical composition

bull Human Capital Development - skills

bull Economic benefits

ndash Commercialization through Licensing

ndash Local Manufacturing

ndash Access fees19

Thank you

Discussion

21

Structure determination of

molecules

bull NMR

bull MS

bull UV IRCD

copy CSIR 2008 wwwcsircozacopy CSIR 2008 wwwcsircoza

HPLC

pumpHPLC column

INJECTION

- Extract

- Fraction

- Mixture

LCMS

INTERFACE

Splitting dependent

of the LCMS

interfaces used

waste

UV

MS

UV

MS

spectra

1

Speed vac -

off-line or on-line

biological assays

2- LCmicro fractionation

Active fractionsemi

pure compounds

Speed vac -

Storage

Structural

information

Separation by HPLCUVMS

Page 17: Creation of a National Compound Library/Biodiversity ... · Creation of a National Compound Library/Biodiversity Market Bank ... knowledge system on the medicinal use of these plants,

Leveraging the Library ndashConservation

bull Trusted collection

ndash No need to recollect samples

ndash Legal controlled access to industry acedemia

ndash Link to IK databases (NIKMAS)

ndash Link to plant distribution maps

ndash One ldquoshop stoprdquo to the world eg pharma

ndash Control of samples leaving the country

ndash Tool for issuing notifications and permits

bull HCD

ndash New skills training for post graduates

bull Food and cosmetics

ndash Growing market for natural ingredients

1717

Possible Model for the Market

bank

National Repository of Biodiversity samples and

Natural Compounds

bull Legal entity

bull Hosted or independent

bull Government control and access

bull Compound production and storage

bull Core Staff

bull Students

Access

Ownership

Science

Councils

Communities

NGOsUniversities

Deposit

samples

Leveraging the Library ndash Health needs

bull Burden of disease in SA

ndash HIV

ndash TB

ndash Cancer

ndash Cardiovascular disease

ndash Diabetes

ndash Malaria

ndash Alzheimerrsquos

bull Life style diseases

ndash Obesity

bull Food and cosmetics

ndash Growing market for natural ingredients

18

Leveraging the Library Socio-economic

bull Local ldquoclearing houserdquo to provide trusted collections

ndash Government approved and compliance

ndash High quality preserved and reproducible

ndash Controlled access

bull Conservation

ndash No need for huge plants collections

bull Agro-processing

ndash Cultivation and processing through local communities

bull IP creation owned by South Africans

ndash Chemical composition

bull Human Capital Development - skills

bull Economic benefits

ndash Commercialization through Licensing

ndash Local Manufacturing

ndash Access fees19

Thank you

Discussion

21

Structure determination of

molecules

bull NMR

bull MS

bull UV IRCD

copy CSIR 2008 wwwcsircozacopy CSIR 2008 wwwcsircoza

HPLC

pumpHPLC column

INJECTION

- Extract

- Fraction

- Mixture

LCMS

INTERFACE

Splitting dependent

of the LCMS

interfaces used

waste

UV

MS

UV

MS

spectra

1

Speed vac -

off-line or on-line

biological assays

2- LCmicro fractionation

Active fractionsemi

pure compounds

Speed vac -

Storage

Structural

information

Separation by HPLCUVMS

Page 18: Creation of a National Compound Library/Biodiversity ... · Creation of a National Compound Library/Biodiversity Market Bank ... knowledge system on the medicinal use of these plants,

Leveraging the Library ndash Health needs

bull Burden of disease in SA

ndash HIV

ndash TB

ndash Cancer

ndash Cardiovascular disease

ndash Diabetes

ndash Malaria

ndash Alzheimerrsquos

bull Life style diseases

ndash Obesity

bull Food and cosmetics

ndash Growing market for natural ingredients

18

Leveraging the Library Socio-economic

bull Local ldquoclearing houserdquo to provide trusted collections

ndash Government approved and compliance

ndash High quality preserved and reproducible

ndash Controlled access

bull Conservation

ndash No need for huge plants collections

bull Agro-processing

ndash Cultivation and processing through local communities

bull IP creation owned by South Africans

ndash Chemical composition

bull Human Capital Development - skills

bull Economic benefits

ndash Commercialization through Licensing

ndash Local Manufacturing

ndash Access fees19

Thank you

Discussion

21

Structure determination of

molecules

bull NMR

bull MS

bull UV IRCD

copy CSIR 2008 wwwcsircozacopy CSIR 2008 wwwcsircoza

HPLC

pumpHPLC column

INJECTION

- Extract

- Fraction

- Mixture

LCMS

INTERFACE

Splitting dependent

of the LCMS

interfaces used

waste

UV

MS

UV

MS

spectra

1

Speed vac -

off-line or on-line

biological assays

2- LCmicro fractionation

Active fractionsemi

pure compounds

Speed vac -

Storage

Structural

information

Separation by HPLCUVMS

Page 19: Creation of a National Compound Library/Biodiversity ... · Creation of a National Compound Library/Biodiversity Market Bank ... knowledge system on the medicinal use of these plants,

Leveraging the Library Socio-economic

bull Local ldquoclearing houserdquo to provide trusted collections

ndash Government approved and compliance

ndash High quality preserved and reproducible

ndash Controlled access

bull Conservation

ndash No need for huge plants collections

bull Agro-processing

ndash Cultivation and processing through local communities

bull IP creation owned by South Africans

ndash Chemical composition

bull Human Capital Development - skills

bull Economic benefits

ndash Commercialization through Licensing

ndash Local Manufacturing

ndash Access fees19

Thank you

Discussion

21

Structure determination of

molecules

bull NMR

bull MS

bull UV IRCD

copy CSIR 2008 wwwcsircozacopy CSIR 2008 wwwcsircoza

HPLC

pumpHPLC column

INJECTION

- Extract

- Fraction

- Mixture

LCMS

INTERFACE

Splitting dependent

of the LCMS

interfaces used

waste

UV

MS

UV

MS

spectra

1

Speed vac -

off-line or on-line

biological assays

2- LCmicro fractionation

Active fractionsemi

pure compounds

Speed vac -

Storage

Structural

information

Separation by HPLCUVMS

Page 20: Creation of a National Compound Library/Biodiversity ... · Creation of a National Compound Library/Biodiversity Market Bank ... knowledge system on the medicinal use of these plants,

Thank you

Discussion

21

Structure determination of

molecules

bull NMR

bull MS

bull UV IRCD

copy CSIR 2008 wwwcsircozacopy CSIR 2008 wwwcsircoza

HPLC

pumpHPLC column

INJECTION

- Extract

- Fraction

- Mixture

LCMS

INTERFACE

Splitting dependent

of the LCMS

interfaces used

waste

UV

MS

UV

MS

spectra

1

Speed vac -

off-line or on-line

biological assays

2- LCmicro fractionation

Active fractionsemi

pure compounds

Speed vac -

Storage

Structural

information

Separation by HPLCUVMS

Page 21: Creation of a National Compound Library/Biodiversity ... · Creation of a National Compound Library/Biodiversity Market Bank ... knowledge system on the medicinal use of these plants,

21

Structure determination of

molecules

bull NMR

bull MS

bull UV IRCD

copy CSIR 2008 wwwcsircozacopy CSIR 2008 wwwcsircoza

HPLC

pumpHPLC column

INJECTION

- Extract

- Fraction

- Mixture

LCMS

INTERFACE

Splitting dependent

of the LCMS

interfaces used

waste

UV

MS

UV

MS

spectra

1

Speed vac -

off-line or on-line

biological assays

2- LCmicro fractionation

Active fractionsemi

pure compounds

Speed vac -

Storage

Structural

information

Separation by HPLCUVMS

Page 22: Creation of a National Compound Library/Biodiversity ... · Creation of a National Compound Library/Biodiversity Market Bank ... knowledge system on the medicinal use of these plants,

copy CSIR 2008 wwwcsircozacopy CSIR 2008 wwwcsircoza

HPLC

pumpHPLC column

INJECTION

- Extract

- Fraction

- Mixture

LCMS

INTERFACE

Splitting dependent

of the LCMS

interfaces used

waste

UV

MS

UV

MS

spectra

1

Speed vac -

off-line or on-line

biological assays

2- LCmicro fractionation

Active fractionsemi

pure compounds

Speed vac -

Storage

Structural

information

Separation by HPLCUVMS