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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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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