Marine pharmacognosy

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MARINE PHARMACOGNOSY
Dr. Arkene Levy
PhD ( Pharmacology), BSc ( Chemistry/Zoology), Cert.
(University Teaching)
LECTURE MATERIALS
1. PowerPoint lecture handout
2. Reading Material
Required:
a. Part A, Sections 3&4. Fundamentals of Pharmacognosy and Phytotherapy-
2nd Edition. (Esp. pg. 131-133)
b. http://www.tandfonline.com/doi/pdf/10.1080/08927014.2014.997226
c. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3944531/**********!!!
LECTURE OBJECTIVES
1. Define Marine Pharmacognosy
2. Describe the history of Marine Pharmacognosy
3. Describe the classification of Marine Drugs according to pharmacological
actions: eg. Antibacterial: Ancanthellin
4. Describe the major sources of Marine natural products eg. Ancanthelin from
sponge (Acanthella acuta)
5.Describe the methods of Collection of Marine Organisms
6.Describe the handling of Marine Organisms
7.Describe the storage of Marine Drugs
MARINE PHARMCOGNOSY
• An area of Pharmacognosy, which studies naturally
occurring substances of medicinal value from marine
sources such as :
Bacteria, virus, algae, fungi, sponges etc.
• 70% of the earths surface covered by ocean: over 300,000
Invertebrates and Algal species
• The marine environment contains roughly 80% of the worlds plant
and animal species
• Early Greek, Japanese, Chinese and Indian civilizations explored
marine life as a source of drugs
• Seaweeds have been used as crude drugs in the treatment of Iodine
deficiency states such as Goiter, sources of vitamins and in the
treatment of Anaemia during pregnancy.
MARINE PHARMACOGNOSY: HISTORICAL OVERVIEW Icelandic kelp 8000 ppm
Norwegian kelp 4000 ppm
Atlantic kelp 2000 ppm
IODINE CONTENT OF SOME SEAWEEDS
KELPS: BROWN ALGAE: PHAEOPHYCEAE
VITAMIN AND IRON CONTENT CONTENT OF SOME SEAWEEDS
Pyropia tenera/Nori
(Bangiaceae/Red Algae)
Vitamins: ABC > 30%
Iron = 14%

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• Exploration of the marine environment increased due to
modern snorkeling, the introduction of SCUBA (1970s), to the
use of manned submersibles (1980s) and more recently the use
of remotely operated vehicles (ROVs) (1990s)
• Advancements in the past 40 years of exploration have
resulted in the isolation of thousands of structurally unique
bioactive marine natural products
MARINE PHARMACOGNOSY: HISTORICAL OVERVIEW
• Marine natural products enclose a wide variety of chemical classes,
including: Terpenes, Polyketides, Acetogenins, Peptides, Alkaloids
• Numerous compounds have been isolated from marine organisms having
different biological activities: antibacterial ,antiviral, antitumour,
antiparasitic, anticoagulants, antimicrobial, antiinflammatory and
cardiovascular compounds.
MARINE PHARMACOGNOSY: HISTORICAL OVERVIEW
TABLE-1 CLASSIFICATION OF MARINE DRUGS
CARDIOVASCULAR Eledoisin, Octapamine
ANTIMICROBIALS/ANTIBIOTICS Acanthellin-1, Pacifenol, Eunicin, Laurinterol, Aeroplysinin-
1, Cephalosporin C, Istamycin A, Istamycin B
ANTI-VIRAL -Acyclovir, ARA-A, ARA-C, Avarol, Dollabelladienetriol
ANTI-FUNGAL Zonarol/isozonarol, sadamycin, geodisterol
ANTI-PARASITIC Kainic acid, Domoic acid
ANTI-CANCER Bryostatin-1, Plitidepsin, Trabectidin, Dolostatin-10
ANALGESIC/ ANTI-INFLAMMATORY Ziconotide, Zonarol, Fucoxanthin
ANTICOAGULANTS Fucoidan
ANTI-SPASMODICS Agelasidine-A
PROSTAGLANDINS PGE-2
MARINE TOXINS Saxitoxin, Holothurin-A
ANTIMICROBIALS
COMPOUND
NAME
BIOLOGICAL
SOURCE
CHEMICAL
STRUCTURE
EFFECTS/USES
Acanthellin-1
(terpene)
Acanthella acuta
(sponge)
Active against
mycobacterium
Pacifenol,
(terpenoid)
Laurencia
Filiformis &
Claviformis
(red algae)
Antimicrobial agent
(Pseudomonas &
Streptococcus)
Eunicin Eunicia
mammosa
(Coral)
Antimicrobial
COMPOUND
NAME
BIOLOGICAL
SOURCE
EFFECTS/USES
Laurinterol Laurencia
johnstonii
(red algae)
Antimicrobial
agent
Aeroplysinin-1 Verongia
Aerophoba
(sponge)
Antimicrobial
agent
Bromopyrones Ptilonia
Australasica
(red algae)
They are toxic as
well as
Antimicrobial
agent.
ANTIMICROBIALS
LAURENCIA SPECIES
• Laurencia is a red algal genus comprising 130 species
• Contains compounds with: antiviral, antibacterial, antifouling,
antifungal, antioxidant, antimalarial, antihelmintic, anti-asthmatic &
cytotoxic activities
Phylum Rhodophyta
Class Florideophyceae
Family Rhodomelaceae
Genus Laurencia

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COMPOUND
NAME
BIOLOGICAL
SOURCE
CHEMICAL
STRUCTURE
EFFECTS/USES
Cephalosporin
-C
(Cefalotin)
Acremonium sp.
(fungus)
Antibiotic agent
(Staph, Strep. E
coli)
Istamycin-A Streptomyces
tenjimariensis
(Bacteria)
Gr(-) and Gr(+)
bacteria.
Istamycin-B Streptomyces
tenjimariensis
Gr(-) and Gr(+)
bacteria.
ANTIBIOTICS
WHAT IS THE MOA OF CEPHALOSPORINS?
• Cephalosporins are bactericidal
• They β-lactam antibiotics, but are less susceptible to
β-lactamases
• Disrupt the synthesis of the peptidoglycan layer
forming the bacterial cell wall
ANTIVIRALS
COMPOUND NAME BIOLOGICAL
SOURCE
EFFECTS/USES
Acyclovir
Ara-A (vidarabine)
Tectitethya
crypta
(sponge)
Herpes, chicken
Pox, shingles
Avarol
(Sesquiterpenoid)
Disidea avara
(sponge)
Activity against HIV
Dollabelladienetriol Sargassum
Binderi
(Brow algae)
Inhibits
HIV-1 RT
DISIDEA AVARA
ACYCLOVIR
• The nucleosides spongothymidine and spongouridine isolated from
Tectitethya crypta formed the substrate for synthesis of acyclovir (as
well as vidarabine and cytarabine(ARA-C/anticancer)
• Family Tethyidae
AcyclovirSpongothymidineSponguridine
COMPOUND
NAME
BIOLOGICAL
SOURCE
CHEMICAL
STRUCTURE
EFFECTS/USES
Zonarol/
isozonarol
Dictyopteris
undulata
(brown algae)
Phytopthera cinnamoni,
sclerotinia sclerotiorum
Sadamycin Streptomyces
Hedaya
(bacteria)
C. albicans, Aspergillus &
Cryptococcus inhibition
Geodisterol
sulfates
Geodia
cydonium
(Sponge)
C. albicans & S.
cerevisiae
ANTIFUNGALS

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COMPOUND
NAME
BIOLOGICAL
SOURCE
CHEMICAL STRUCTURE EFFECTS/ USES
Bryostatin-1 Bugula neritina
(Bryozoa/moss
animal)
lymphocytic
leukaemia
lung, prostate and
non-Hodgkin's
lymphoma**
MOA: Potent modulator of protein kinase C : inhibit cell growth and
angiogenesis and induces apoptosis
ANTICANCER AGENTS BUGULA NERITINA
https://www.youtube.com/watch?v=qx0kA8LJNvc
COMPOUND
NAME
BIOLOGICAL
SOURCE
CHEMICAL STRUCTURE EFFECTS/USES
Plitidepsin
(peptide)
Alpidium albicans
(Ascidian/Sea
Squirts)
Hematological
Cancers Eg. CLL
MOA: . Induces tumor cell death via caspase dependent apoptosis
(programmed death)
As of 2007, undergoing phase II clinical trials, In 2003, granted orphan
drug status by the European Medicines Agency for treating acute
lymphoblastic leukemia
ANTICANCER AGENTS
PLITIDEPSIN: Besides inducing apoptosis of Chronic Lymphocytic
Leukemia (CLL) cells, Plitidepsin also acts on monocytes and
Nurse-Like cells (NLCs). NLCs promote survival of CLL cells by
releasing pro-survival factors
COMPOUND
NAME
BIOLOGICAL
SOURCE
CHEMICAL STRUCTURE EFFECTS/ USES
Trabectidin
Ecteinascidia
turbinata
(Sea Squirt)
Soft tissue sarcoma
patients &
In combination with
doxorubicin for relapsed
platinum-sensitive ovarian
cancer patients
MOA: Transcription inhibition, alters tumor biology, and induces the resumption
of natural cellular differentiation in sarcomas
ANTICANCER AGENTS
TRABECTIDIN: acts on the tumor microenvironment by directly
affecting monocytes and TAMs or indirectly by inhibiting the secretion
of inflammatory mediators eg. CCL2

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COMPOUND
NAME
BIOLOGICAL
SOURCE
CHEMICAL
STRUCTURE
EFFECTS/USES
Dolostatin-
10
Dolabella
auricularia
(Sea Hare/
Mollusc)
Breast and liver
cancers, solid
tumors and
some leukemias.
MOA: Inhibits microtubule assembly. In Clinical Trials
ANTICANCER AGENTS ANTISPASMODIC
COMPOUND NAME BIOLOGICAL
SOURCE
CHEMICAL
STRUCTURE
EFFECTS/USES
Agelasidine-A
(terpene) Agelas
clathrodes
(Sponge)
It has very
potent
Antispasmodic
activity
Antibacterial
activity against
Staphylococcus
aureus
COMPOUND NAME BIOLOGICAL
SOURCE
CHEMICAL
STRUCTURE
EFFECTS/USES
Eledoisin Eledone muschata
(Cephalopod/Octo
pus )
Vasodilation
Octapamine Octopus vulgaris
(Octopus )
Also found in bitter orange
Sympathomimetic
/used in weight
loss supplements
CARDIOVASCULAR AGENTS
COMPOUND
NAME
BIOLOGICAL
SOURCE
CHEMICAL
STRUCTURE
EFFECTS/ USES
Ziconotide
(peptide)
Conus Magnus
(Sea snail)
Analgesic( non-
opioid) : Severe
chronic pain
refractory to
morphine (IT)
MOA: Calcium channel blocker: inhibits the release of pro-nociceptive
neurochemicals eg. substance P in the brain and spinal cord
ANALGESIC
COMPOUND
NAME
BIOLOGICAL
SOURCE
CHEMICAL STRUCTURE EFFECTS/ USES
Zonarol
(Terpene)
Dictyopteris
undulata
(brown algae)
Analgesic :
Severe chronic
pain refractory
to morphine
Fucoxanthin
(terpene)
Most brown
algae
Eg. Sargassum
sp
COX, NO, PG
Inhibition
ANTI-INFLAMMATORY AGENTS
COMPOUND
NAME
BIOLOGICAL
SOURCE
CHEMICAL STRUCTURE EFFECTS/USES
Fucoidan
(Sulphated
polysacahride)
Fucus
vesiculosus
(brown algae )
Thrombin
inhibition by
heparin cofactor
II.
ANTICOAGULANTS

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PROSTAGLANDINS
COMPOUND
NAME
BIOLOGICAL
SOURCE
CHEMICAL
STRUCTURE
EFFECTS/USES
PGE2 Gracilaria
verucossa
(Red algae)
Active CNS agent
Oxytoxic &
Abortifacient
Suppress blood
platelet
aggregation
ANTIPARASISTICS
COMPOUND NAME BIOLOGICAL
SOURCE
CHEMICAL
STRUCTURE
EFFECTS/USES
kainic acid
(pyrolidine)
Digenia simplex
(red algae)
Anthelmintic
(round, tape
worms)
Convulsant
Domoic acid
(kainic acid
analog)
Chondria armata
(red algae)
Neurotoxin**
History of
poisoning
Canada (1987)
COMPOUND
NAME
BIOLOGICAL
SOURCE
CHEMICAL STRUCTURE EFFECTS/USES
Saxitoxin Alexandrium sp
(dinoflagellate)
Blocks Na*
channels on
neurons: Flacid
paralysis
Holothurin-A Helixpomatia
(sea cucumber)
• Haemolytic
activity
• Antifungal
activity.
MARINE TOXINS OMEGA THREE FATTY ACIDS: FOR
HYPERTRIGLYCERIDEMIA
• Lovaza: synthesized from ,Mackerel and Anchovy oil
• Contains:
Eicosapentaenoic acid ethyl ester
Docosahexaenoic acid ethyl ester
• It is a pro-drug that is metabolized into Omega-3 FA
• Indications:
 Hypertriglyceridemia, monotherapy, or + statin
 Secondary prevention after myocardial infarction
Engraulis sp
Rastrelliger sp
LOVAZA MOA
• Decreased lipogenesis in the liver
• Increased plasma lipoprotein lipase activity
• Note: MOST DRUGS LIKE THIS INCREASE LDL SO
NOT USED FOR HYPERCHOLESTERMEIA
PROTOCOLS FOR MARINE R&D
1
• Collection & field identification of the Marine organisms
• Preparation of extracts from organism
2
• Biological assay of the extract
• Activity directed separation
3
• Purification of active ingredient

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• Many marine species are to toxic humans
• Caution should always be taken in handling marine organism.
• Proper protective equipment such as Gloves & Goggles should always be
worn
• Some sponges have highly irritating compounds that cause immediate
itching & ash formation in some individuals
Eg. Tedania ignis (fire sponge)
HANDLING MARINE ORGANISMS FIRE SPONGE
Smithsonian tropical research institute
• Collection of organisms should be documented
• Record the longitude, latitude, depth, water temperature, salinity
and dates of collection.
• Habitat of collection (eg:in crevice, Under rock)
• Careful description of organism like color, odor, morphology, the
presence of associated Organism inside or outside should be noted
• Voucher specimens should be prepared to allow for complete
identification
COLLECTION OF MARINE ORGANISMS
• Marine Organisms are often collected at remote places where
laboratory facilities are limited.
• Many rapidly begin to decompose, therefore Organisms need to be
either dried, extracted or frozen immediately to reduces spoilage &
chemical degradation.
• Sponges, can begin to degrade and polymerize immediately up on
being touched.
• After collection the organisms should be frozen immediately at-20˚C.
In some cases, organisms are placed into an alcohol such as
methanol, ethanol or Isopropanol.
STORAGE OF MARINE ORGANISMS
QUESTION
Which one of the following anticancer marine drug
modulates protein kinase release ?
a) Bryostatin-1
b) Plitidepsin
c) Trabectidin
d) Dolostatin-10
• Acremonium sp is the biological source of:
a. Istamycin
b. Cephalosporin
c. Acyclovir
d. Sasitoxin