Pharmacognosy -2 PHG 322 - psau.edu.sa · Pharmacognosy -2 PHG 322. The marine biosphere Marine...

Prof. Dr. Amani S. Awaad

Professor of PharmacognosyPharmacognosy Department,

College of Pharmacy Salman Bin Abdulaziz

University,

Al-Kharj. KSA.

Email: amaniawaad@hotmail.com

Pharmacognosy -2

PHG 322

The marine biosphere

Marine secondary metabolites

biological activities Marine secondary metabolites

Some marine comopounds

Marine Natural

Products

5

• More than 70 % of the planet’s surface is covered by oceans.

• The great biodiversity of marine environment.

• More than 300 000 species of plants and animals are described.

• Great number of marine organism have no terrestrial counterparts.

• The very special living condition for marine organisms led them to adapt different physiological and behavioural characters which consequently resulted in novel biologically active molecules.

• Sea organisms are mostly unexplored reservoirs of new drugs.

• A small number of marine plants, animals, and microbes have already yielded more than 12000 novel chemicals.

• Hundreds of new compounds still being discovered every yea

Marine Natural Products

Importance of marine environment

Phases of work on marine chemistry

Marine Natural Products

In the 1950’s researchers were interested in

studying the marine spines and shells of sea

urchins with beautiful colors.

In the 1970’s interest of researchers was

attracted to the halogenated metabolites from

red algae.

From the 1980’s till now the marine

chemistry was directed by the currently used

sophisticated and smart biological assays.

Interest switched from marine algae to

marine invertebrates.

Marine Natural Products

Problems of marine research

1- The lack of trained personal.

2- Diving hazards.

3- The marine trips are effort, time and money consuming.

4- The time consuming experiments.

5- The scarcity of the starting organism to carry out the

complete study.

6- Recollection problems of the same organisms in the

dynamic environment.

7- Difficulties in culturing of marine organisms in the lab.

8- Most of the marine secondary metabolites are polar

compounds, so additional difficulties with extraction,

fractionation and separation are faced.

9- The marine organisms are usually associated with parasitic

commensal or symbiotic flora.

10- The lack of folk medicine information or ethnobotanical

documentation.

Marine Natural ProductsThe marine biosphere

Marine organisms are classified into the following

phyla: 1)Monera, 2)Protista, 3)Metazoa,

4)Higher plants

* Monerans are one-celled organisms that have no nucleus or organelles.

*Monerans are individual cells that survive on their own.

*They do not work together in groups. However, they can be found in

pairs, clumps, or in chains.

*The kingdom of Monera is divided into two types or

organisms, bacteria and cyanobacteria.

1) Monera

*They make their own food through the process of photosynthesis.

*These cells are found in oceans, lakes, ponds, swimming pools, and

moist soil.

*They are an important food source for many of the animals in the

water.

*They can be found alone, in colonies, or long thread like chains.

Cyanobacteria (blue-green algae )

Marine Natural ProductsThe marine biosphere

2) Protista

a diverse group of eukaryotic microorganisms.

unicellular, or multicellular without specialized

tissues.

They include ; a-marine fungi and b-algae.

A-marine fungi

live saprophytic on algae, plants or

animals.

parasites on shells, crabs, sponges, in the

GIT of fishes.

Or symbiotic as in lichens.

Source of antibacterial, antifungal,

cytotoxic and anti-inflammatory agents.

produce several secondary metabolites e.g.

alkaloids, terpenoids and polyketides.

Marine Natural ProductsThe marine biosphere

2) Protista

b-algae

are a large and diverse group of simple,

typically autotrophic organisms, ranging

from unicellular to multicellular forms.

They are photosynthetic and simple.

There are nearly 30,000 algae species.

They could be divided into the

following groups:

1- Red algae (Rhodophyta)

2- Brown algae (Phaeophyta)

3- Green algae (Chlorophyta)

4- Golden brown algae

5- Yellow algae and diatoms

(Chrysophyta)

6- Euglenophyta

7- Blue green algae

8- Dinoflagellates (Pyrrophyta)

Chlorophyta (green algae):About 8000 species.

Mostly live in fresh water. Chlorophyll a and c.

Rhodophyta (red algae) About 5000 – 6000

species.95% are marine.Chlorophyll a, phycoerythrin.

Phaeophyta (brown algae) About 1500-2000 species.99%

are marine.Chlorophyll a, c and phycoerythrin

Marine Natural ProductsThe marine biosphere

3)Metazoa(Marine animal)

Marine vertebrates and invertebrates were subjected to chemical

study.

These studies covered representative phyla:

Porifera ,Cnidaria, Mollusca, Chordat, Echinodermata,Annelida,

Over 9000 known species. Aquatic sessile filter feeders.

50% of the natural products reported from marine invertebrates.

About 2600 metabolites were isolated.

a)Porifera (Sponges األسفنج)

b)Cnidaria

This phylum include: soft and hard

corals, gorgonians, sea pens, jellyfish,

sea wasps and sea anemones.

Sea pens Corals المرجانSea anemones

شقائق النعمانJellyfish قنديل البحر

Marine Natural ProductsThe marine biosphere

3)Metazoa(Marine animal)

c)Mollusca الرخويات

This phylum contains a highly diverse group of

animals including 50000 species and 60000 fossil

molluscs. snails الحلزون , tusk shells, shellfish المحار ,

octopus اإلخطبوط , squids حبار , mussels بلح البحر

d)Chordata حبليات

This phylum includes tunicates and vertebrates. The most

distinctive morphological features of chordates are the

notochord, nerve cord, and visceral clefts and arches.

e)Echinodermata قنفذيات او شوكيات

With 7000 extant and 13000 extinct species.

Marine Natural Products

Marine secondary metabolites

During the last 30-40 years numerous novel compounds have been isolated from

marine organisms having biological activities such as Antibacterial, Antiviral,

Antitumer, Antiparasitic, Anticoagulants, Antimicrobial, Anti-inflammatory and

cardiovascular active products.

•Antimicrobial agent and

antibiotics

•Antiviral compounds

•Antiparasitic agents

•Anticancer agents

•Anticoagulant agents

•Cardiovascular and

Neurophysiological agents

•Anti-inflammatory and

Antispasmodic agents

Marine Natural ProductsMarine secondary metabolites

1)Antimicrobial agent and antibiotics

•Cephalosporin: It is obtained from the

marine fungus, Cephalosporium acremonium. It

has been widely used as an antibiotic drug active

against microbes insensitive to penicillin and

ampicillin.

•Istamycins: This is the fermentation product of

marine microorganisms Strptomyces lenjimariesis.

•Zonarol and Isozonarol: They are both

obtained from Dictyopteris zonaroides (Brown

algae). They are used as antimicrobial agents.

•Halotoxin A, B, C: It is obtained from the

Stichopus japonicas ( Sea cucumber). It is

antifungal in nature.

•Ircinin: It is obtained from the Ircin oros.

Zonarol

Marine Natural ProductsMarine secondary metabolites

1)Antimicrobial agent and antibiotics

Squalamine

• is the first aminosterol isolated from the dogfish

shark Squalus acanthias (squalidae).

• It has potent antimicrobial activity against

Staphylococcus aureus and antitumour properties.

• in clinical trials for the treatment of advanced

non-small-cell lung cancer.

Cribrostatins

• isolated from a blue sponge Cribrochalina sp.

and showed potent antineoplastic and

antimicrobial activities.

• Cribrostatin 3 has potent inhibitory activity

against penicillin- resistant Neisseria gonorrheae

Dogfish shark

N

O

O

O

CH3

H3C

C2H5O

Cribrostatine 2

Cribrochalina sp.

Marine Natural ProductsMarine secondary metabolites

2)Antiviral compounds

•Ara-A: a semi-synthetic substance based on

the arabinosyl nucleosides, isolated from the

Tethya crypta.

•Avarol and Avarone: It is obtained

from the sponge, Disidea avara. These

compounds inhibit the immunodeficient virus,

have high therapeutic indices and the ability to

cross blood brain barrier (bbb). These

compounds have potential use in the treatment

of AIDS.

•Eudostomin-A: It is obtained from the

Eudostoma olivaceum.

•Patellazole-B: It is obtained from the

Ascidian lissocilium patella. has very potent

in vitro activity against herpes simplex

viruses.

H OH

OH

Avarol

H

6` 4`

O

O

Avarone

Eudistoma olivaceum

Tethya sp.

Ara-A

Marine Natural Products

Marine secondary metabolites

3)Antiparasitic Compounds

- Domic acid: It is obtained from the red

algae, Chondria armata. It is used as

anthelmintic.

- Cucummechinoside-F: It is obtained

from the sea cucumber. It is used as

antiprotozoal activity.

- Bengamide-F: It is obtained from the

sponges, nudibranch and a zoanthid.

- Laminine: It is obtained from

Laminaria angustata. It is use as an

anthelmintic as well as smooth muscle

relaxant.

Domic acid

Bengamide-F

Marine Natural Products

Marine secondary metabolites

4)Anticancer agents

• Sinularin: It is

obtained from the Sinularia

flexibilis.

• Halitoxin: It is

obtained from the helieloma

viridis.

• Tocotrienol: It is obtained

from brown algae, Sargassum

tortile.

• Geranylhydroquinone : It

is obtained from the chloform

extract of Aplidium species.

Sinularin

HalitoxinTocotrienol

Geranylhydroquinone

Marine Natural Products

Marine secondary metabolites

5)Anticoagulant agents

•Carageenan: It is obtained

from the Chondrus, Euchauma and

Gigrtina. It is reported

anticoagulant activity.

•Galaxtan sulphuric acid: It is

obtained from the Irdaea

laminaroides.

Marine Natural Products

Marine secondary metabolites

6)Cardiovascular and Neurophysiological agents

• Eldoisin: It is obtained from the

Eledone moschata (cephalopod). It is powerful

hypotensive compound obtained from posterior

salivary gland of cephalopod.

• Octapamine: It is obtained from the

Octopus vulgaris, O. Macropus and E. Moschata.

Its gives cardiovascular and adrenergic response.

• Tetramine: It is obtained from the Naptunea

antique. It shows curare like Effect.

• Laminine: It is obtained from the Laminaria

angustata. It is used as hypotensive agent.

Marine Natural Products

Marine secondary metabolites

7)Anti-inflammatory and Antispasmodic agents

• Manoalide: It is obtained from the

Luffariella variabilis. It is act by direct

inactivation of phospholipase A2, which is

present in some neurotoxins and also has a

role in synthesis of PGs in humans.

• Tetradoxin: It is obtained from the

puffer fishes Spherides rubripes. It is used

as strong antispasmodic.

• Flustramine A and B: It is

obtained from the Flustra foliaceal

(Swedish marine moss animal). It is used

as muscle relaxant.

O

O

HO

HO

O

Manoalide

Flustra folia