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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5924_Библиотеки_им_академика_М_И_Перельмана.pdf
208 Textbook of Pharmacognosy and Phytochemistry I
Structures of compounds in Table 10.1
Marine Pharmacognosy (Novel Medicinal Agents from Marine Source) 209
ANTIVIRAL COMPOUNDS
Many marine microorganisms have been
screened for antiviral activity and wide range
of active compounds have been reported, but
only few compounds are reported to have
significant therapeutic activity and these are:
Antiviral and Anti HIV agents: Laminaran
species from brown algae are reported to have
antiviral, anti HIV and anticoagulant activity.
Ara-A (Fig. 10.7): It is a semi-synthetic compound based on the arabinosyl nucleosides
isolated from the sponge Tectitethya crypta.
Fig. 10.7: Ara-A (vidrabine)
Fig. 10.9: Eudistomin A
Laurenterol (Fig. 10.10) possessing antibacterial activity against gram-positive bacteria
obtained from Laurencia spp. (Ophioderma
variegatum) and from the sea hare Aplysia
californica.
Fig. 10.10: Laurenterol
Oppositol (Fig. 10.10a) antibacterial agent
from Laurencia suboppostia; against Staphylo-
coccus aureus.
Avarol and Avarone (Fig. 10.8): These compounds (sesquiterpene hydroquinone) are
isolated from a sponge, Dysidea avara schmidt.
These compounds inhibit the immunodeficiency virus, have high therapeutic indices
and the ability to cross blood–brain barrier.
Fig. 10.8: Avarol and avarone
Didemnins: These are cyclic depsipeptides
isolated from tunicate, Tectitethya crypta.
β
Eudistomin A (Fig. 10.9) and
-Carbolines:
This is also isolated from tunicate, Eudistoma
olivaceum.
Fig. 10.10a: Oppositol
Patellazol B (Fig. 10.11) isolated from the
tunicate, Lissocilium patella has very potent in
vitro activity against Herpes simplex viruses.
CYTOTOXIC COMPOUNDS
Large number of compounds isolated from
marine organisms have been tested for
cytotoxicity in the search for drugs active
against cancer. Among all, the best known
novel compounds with high potential as
anticancer drugs are found to be macrolides,
known as bryostatins isolated primarily
from the bryozoan, Bugula neritina and later
some have been extracted from sponges and
tunicates.
210 Textbook of Pharmacognosy and Phytochemistry I
Fig. 10.11: Patellazol B
Many Bryostatins (1–18) are reported to
have antileukaemic activity but only Bryostatin1 and Bryostatin-2 have undergone phase
2 clinical trials.
Bryostatin (Fig. 10.12) triggers activation and
differentiation of peripheral blood cells from
lymphocytic leukemia patients. It also causes
activation of protein kinase C and arachidonic
Fig. 10.12: Bryostatin-I
acid metabolite release. Both Bryostatin 1 and
2 enhance the efficiency of interleukin-2, in
initiating the development of in vivo primed
cytotoxic T-lymphocytes.
Dolastatins is a family of cyclic and linear
peptides and depsipeptides; isolated from the
sea hare, Dolabella auricularia. The highly
cytotoxic compounds are Dolastatin 10,
Dolastatin-H and Isodolastatin-H (Fig. 10.13).
In addition to the peptides, the polypropionate,
Antipyrone A and B have also been extracted
from D. auricularia.
Fig. 10.13: Dolastatins and isodolastatin
Marine Pharmacognosy (Novel Medicinal Agents from Marine Source) 211
Eleutherobin is a compound obtained from a
marine encrusting gorgonian Erythropodium
caribaeorum. It is extremely potent for inducing
in vitro tubulin polymerisation and is toxic to
cancer cells with an IC-50 similar to that of taxol.
Xenia a novel diterpene called xenicane iso-
lated from the soft coral Xenia elongata. This
compound has shown some effectiveness in
inhibiting mitochondria respiration in cancer cells.
Nephthea: The soft Coral Nephthea reported
to contain a bioactive compound Lemnabourside
which is 5 alpha-reductase inhibitor. It is quite
active in prostate cancer cells, as they tend to
be androgen dependent. The drug possess
ability to inhibit the conversion of testosterone
into more potent dihydrotestosterone.
Halimide: A low molecular pectin like molecule isolated from green algae Helimeda
opuntia, used in the treatment of early stage
cancer, particularly breast cancer resistant to
current chemotherapy.
Ecteinascidin 743 (ET-743), a natural new
product isolated from the Caribbean sea squirt.
It is totally novel and different from existing
anticancer drugs. ET-743 have shown high
activity in cases of advanced sarcoma, that had
relapsed or were resistant to conventional
therapy.
Yondelis TM (ET-743): Yondelis TM is a new
antitumour drug derived from the marine
organism Ecteinascidia turbinata a ‘Sea Squirt’
or tunicate found in the Caribbean and Mediterranean sea. It is still at the stage of being an
investigational drug and it has been suggested
(USA) that drug is quite useful in the treatment
of patient with advanced sexually transmitted
diseases (STD) after failure of conventional
chemotherapy.
Aplidine: Spanish biotechnology firm Zeltia,
developed this drug from a marine organism,
Mediterranean tunicate Aplidium albicans,
against medullary thyroid carcinoma.
It is reported that Aplidin, a novel antitumour
agent of marine origin undergoing phase II
clinical trials, induces growth arrest and
apoptosis in human MDA-MB-231 breast
cancer cells at nanomolar concentrations.
Ara-C a potent inhibitor of tumour such as
Sarcoma-180, Erlich carcinoma and L-1210 leukaemia in mice. It is also reported to be active
against acute myelogenous leukaemia and
human acute leukaemia. It is one of the
standard drugs used in the treatment of acute
leukaemia; both in children and adults.
Ara-C is a semi-synthetic drug originated
from the Caribbean sponge, the basic compound was spongothymidine, which led to
the synthesis of 1-
αα
α-D-arabinofuranosyl
αα
cytosine (Ara-C), developed and marketed
by Upjohn Pharmaceutical Company as Cytosar.
Ara-A: It is another synthetic analogue to
adenine arabinoside, of Ara-C compound. The
reports says the compound to be effective for
the treatment of Herpes encephalitis.
Asperidol: It is a non-lactonic cembranoid obtained
from gorgonian coral, have anti-cancer activity.
Aplysistatin (LSV) an antileukaemic agent
obtained from sea hare Aplysia angasi.
Dola-triol (LIV): Active antileukaemic agent
possessing different diterpenoid ring system
has been reported from the Indian Ocean sea
hare Dolabella auricularia Holothurin. It is a
toxic triterpenoid glycoside obtained from sea
cucumbers belonging to phylum Echinodermata
(Actinopyga agassizi) are reported to inhibit the
growth of sarcoma-180 and adenocarcinoma
in mice.
Thelothurin A and thelothurin B:
These both
are cytotoxic saponin obtained from sea
cucumber Thelenota ananas.
Spongouridine isolated from Caribbean
sponge Cryptotethya crypta, has shown promising
antiviral and antitumour activities.
Tocotrienol (Lx): An antitumour compound,
isolated from water soluble extract of Sargassum
tortile (brown algae).
CARDIOVASCULAR AND NEUROPHYSIOLOGICAL AGENTS
Anthopleurin A is a heart stimulant possessing
four times more activity than natural cardiac
glycosides (digitalis and strophanthus). It is a
polypeptide in nature, isolated from sea
anemone Anthopleura xanthogrammica.
212 Textbook of Pharmacognosy and Phytochemistry I
Eledoisin is a peptide obtained from posterior
salivary glands of Eledone spp. Eledone moschata
and related species. It is fifty times more potent
than acetylcholine, histamine or bradykinin
ion provoking hypotension. It is a potent
vasodilator and hypotensive agent.
Eptatretin is a potent cardiac stimulant, having
direct action on mammalian myocardium as
produced by epinephrine and digitalis glycosides. It is obtained from aneural bronchial
heart of the Pacific hagfish Eptatretus stoutii.
D-octopamine is an amine found in salivary
glands of Octopus spp. O. vulgaris, O. macropus
and Eledone moschata. It is a potent cardiotonic.
Laminin belongs to heterotrimeric glycoproteins and is obtained from marine algae
Laminaria angustata.
It has potent hypotensive effect on mammals.
Tetrodotoxin is a toxin but possessing cardiovascular and neurophysiological activities. It
is obtained from the skin and testis of Goby,
Gobius criniger; and also from the skin of male
and female Costa Rican frog, Atelopus chiriquiensis.
αα
α-Conotoxin,
αα
κκ
κ-conotoxin
κκ
αα
α
-Conotoxin is obtained from C. figulinus. It is
αα
ωω
ω-conotoxin,
ωω
μμ
μ-conotoxin and
μμ
used in stroke, Parkinson’s disease as muscle
relaxant, antihypertensive agents and analgesic.
ωω
ω
-Conotoxin is obtained from C. geographus.
ωω
It is used to block neuronal calcium channels
at pre-synaptic terminal of neuromuscular
junction like nifidipine and nitradipine.
μμ
μ
-Conotoxin is also obtained from C. geogra-
μμ
phus and used in ischaemia.
κκ
κ
-Conotoxins blocks potassium channel and
κκ
is used in hypertension, arrhythmia and asthma.
ANTI-INFLAMMATORY AGENTS
Pseudopterosins
These are the group of diterpene glycosides. The
pseudopterosins-1 and seco-pseudopterosins-3
were isolated from Caribbean octocorals but are
found in small quantity. Both have shown
more potent anti-inflammatory activity in
comparison to indomethacin.
Marine bi-indole
The bi-indole compound is obtained from
Rivularia firma (Marine cyanobacterium) and
is quite potent anti-inflammatory compound
active in both, the carrageenan (Sulphated
polysaccharide carrageenan) induced rat
paw oedema and kaolin induced rat
paw oedema (Non-immune inflammatory
response).
Manoalide
It is a non-steroidal anti-inflammatory and
painkiller compound obtained from marine
sponge Luffariella variabilis.
Dendalone-3-hydroxy-butyrate
It is marine anti-inflammatory agent
obtained from sponge Phyllospongia dendyi
var frondosa.
Tetrabromo heptanone has been isolated
from red algae.
ANTHELMINTIC
Kainic Acid (C10H15NO4)
A valuable anthelmintic used clinically in
Japan against parasitic roundworm, tapeworm
and for the treatment of ascariasis. It is obtained
from red algae (dried) Digenea simplex.
Domoic Acid (C15H21NO6)
It is obtained from red algae chondria armata.
It is also used in the treatment of ascariasis
and is effective in expelling another parasite
pinworm.
ANTICOAGULANTS
Acanthaphora from red algae contain Laminaran
sulphate used as anticoagulant.
Carrageenan
Carrageenan isolated from species of Chondrus,
Eucheuma and Gigartina, reported to have anti-
coagulant activity.
Laminarin
A highly sulphated laminarin (polysaccharide
from marine algae) has been reported to have
anticoagulant activity.
Marine Pharmacognosy (Novel Medicinal Agents from Marine Source) 213
PROSTAGLANDINS
The term prostaglandin is often abbreviated
as PG, PGE
, denotes a prostaglandin of the E
2
series with two double bonds.
Prostaglandins are a family of cyclic oxygena-
ted, C
fatty acid (prostanoic acid, (Fig. 10.14)
20
derivative substances which consist of a
cyclopentane ring with two side chains having
7 and 8 carbon atoms, respectively. The carboxylic
group is present on C
chain and a C8 chain
7
with methyl terminus. Prostaglandins are
biosynthesised from three essential fatty acids,
8,11,14
eicosatrienoic (dihomo-γ-linolenic acids),
Δ
5,8,11,14
Δ
acid) and Δ
eicosatetraenoic acid (arachidonic
5,8,11,14,17
eicosapentaenoic acid,
which yield prostaglandins of the 1-, 2- and 3series respectively known as PGE
(Fig. 10.15).
PGE
3
, PGE2 and
1
Fig. 10.14: Prostanoic acid
Name prostaglandins was given due to the
fact that they were first discovered in seminal
fluid, although later on, it was reported that
they are not only produced in the prostate
gland but occur practically in all mammal
organs although in very small amounts. PGE
and PGF1 were initially isolated from sheep
seminal plasma but these compounds and
, PGE2 and PGF2a are widely distributed.
PGD
2
Animal source cannot supply sufficient
amounts for drug usage. The soft Coral
Plexaura homomalla (sea whip) from Caribbean
has been reported to have very high (2–3%)
level of prostaglandin esters, predominantly,
the C-15 epimer of PGA
(1–2%) with related
2
structures. Prostaglandins of A-, E- and F-type
(Fig. 10.16) are widely distributed in soft
corals, especially Plexaura. Although some
synthetic prostaglandins are also available,
but it is reported that biological activity
is effectively confined to the natural
enantiomers; the Unnatural enantiomers of
had only 0.1% of the activity of the
PGE
1
natural isomer.
1
Fig. 10.15: Biosynthesis of PGE1, PGE2 and PGE
Prostaglandins constitute a group of
biologically potent substances of wide spectrum
3
214 Textbook of Pharmacognosy and Phytochemistry I
Fig. 10.16: Prostaglandins of A-, E- and F- type
activity. It causes contraction and relaxation
of smooth muscle of the uterus, cardiovascular
system, the intestinal tract and of bronchial
tissue. They may also inhibit gastric acid
secretion, control blood pressure and suppress
blood platelet aggregation.
As such they are inactive but on modification, the inactive compounds become
active. Six different series (A-E) produced by
modification of the cyclopentane ring are now
available as synthetic products. They can be
useful in birth control, induced child birth,
abortion, menstruation problem, peptic ulcers,
treatment of asthma, regulation of blood
pressure and tranquillising effect on CNS.
15-epi-PGA
acetate, methyl ester derivative,
2
obtained from the caribbean gorgonial Plexaura
homomalla in high concentration. Some prosta-
glandins have also been isolated from red
algae Gracilaria lichenoides, i.e. PGE
, which
2
have antitumour activity. The inactive 15-epi
PGA2 and its diester have been converted into
useful prostaglandins (15s) PGA
. Active (15s) PGA2 and (15s) PGE
PGE
2
and (15s)
2
identical to prostaglandins derived from
mammalian sources has been isolated from
P. homomalla collected from different location.
FURTHER READING
1. Costello MJ, Chaudhary C. Marine Biodiversity,
Biogeography, Deep-sea Gradients, and Conservation. Current Biology. 2017;27(23):2051.
2. Evans WC. 2009. Trease and Evans Pharmacognosy,
10th edition, Elsevier, New York.
3. Kalia AN. Textbook of Industrial Pharmacogonsy.
(2005). CBS Publishers and Distributors, New Delhi.
4. Mayer AMS, et al. Marine Pharmacology in 2012–
2013: Marine compounds with antibacterial,
antidiabetic, antifungal, anti-inflammatory,
antiprotozoal, antituberculosis, and antiviral
activities; Affecting the immune and nervous
systems, and other miscellaneous mechanisms
of action. Marine drugs. 2017; 29;15(9).
2
Index
Abbe’s camera 70
Abscisic acid 87
Acetyl value 197
Acid
number 197
value 50
Adulteration 28
Agar 13, 187
Alkaloids 141
Allergens 172
Allergy 172
Allopathy 136
Alloploids 84
Almond oil 199
Anemophilous 174
Angiosperms 20
Anisocytic 66
Anomocytic 66
Anthelmintic 212
Anticoagulants 212
Anti-inflammatory agents 212
Antimicrobial compounds 206
Antiviral compounds 209
Ara-A 208
Arachidonic acid 213
Autoploid 84
Auxins 85
Avarone 208
Ayurveda 135
Baljet test 148
Balsams 14
Bark 11, 42
Bassorin 13, 186
Bees wax 203
Berry 40
Borax test 185
Borntrager test 157
Bromelain 192
Budding 80
Callus 106
culture 115
Camera lucida 69
Cantharidin 7
Carbohydrates 183
Cardiovascular and neuro-
physiological agents 211
Carnauba 203
Carrageenan 52, 212
Casein 190
Catechu 12
Chaulmoogra
acid 198
oil 198
Chemotaxonomy 23
Churus 171
Cochineal 7
Cod liver oil 200
Conotoxin 205
Conservation 92
Cotton 167
Crude drugs 3
Cryopreservation 93
Cuoxan solution 167
Cytokinins 86, 109
Cytotoxic compounds 209
Diacytic 66
Diadelphous 39
Dioscorides 3
DMT 170
Dragendorff’s reagent 50, 144
Ebres papyrus 75
Edible vaccine 128
Entomophilous 175
Essential oil 158
Ester value 51
Ethylene 87
Explant 104
Extracts 12
Feigl-anger 152
Fermentation 88
Galls 7
Gelatin 189
Ghati gum 185
Gibberellins 85
Glycosides 146
Gold beater skin test 162
Gootee 80
Gorlic acid 198
Grafting 80
Growth
hormones 116
regulators 84
Gums 13
acacia 13
Haffner’s method 54
Hager’s reagent 50
Hairy roots culture 113
Hallucinogens 169
Honey 7, 188
Hybridisation 84
Hydnocarpic acid 198
Hydrous wool fat 201
Ichthammol 7
Inflammation 51
Introduction 204
Iodine value 51
Istamycin 206
215
216 Textbook of Pharmacognosy and Phytochemistry I
Juices 12
Keller-killiani 148
Kinetin 86
Lard 200
Latex 12
Layering 79
Legal test 148
Liebermann-Burchard test 150
LSD 170
Lycopodium 63
Lyophilisation 89
Matchstick test 162
Mayer’s reagent 144
Micronutrients 106
Micropropagation 80, 127
Millon’s reagent test 190
Molisch
reagent 147
test 147, 184
Monadelphous 39
Mutation 83
OGTT 55
Oligosaccharides 183
Organized drug 10
Organoleptic 30
Pain 53
Palisade ratio 65
Paracytic 66
Pepo 40
Pepsin 193
Perianth 38
Pharmacognosy 3
Pollens 174
Polyploidy 83
Polysaccharides 183
Pome 40
Propagation 78
Prostaglandins 213
Proto alkaloids 141
Protoplast culture 113
Pseudoalkaloids 141
Pseudopterosins 212
Pteridophytes 20
Raymond test 148
Resins 13
Salkowski reaction 150
Sapogenins 149, 151
Saponification value 51, 197
Serotaxonomy 26
Shinoda’s test 154
Sophistication 29
Sorosis 41
Soxhlet 45
Spermaceti 202
Stomatal
index 64
number 64
Suet 201
Sugars 183
Suspension culture 117
Syconus 41
Tragacanthin 186
Tannins 161
Teratogens 171
Test 152
Thallophytes 20
Tissue culture 97
Totipotency 81
Tragacanth 13, 186
Tragacanthin 13
Trichomes 66
Triton 57
True alkaloids 141
Turpentine 14
Types of plant 112
Unorganized drugs 12
Urokinase 194
Vegetative propagation 79
Vein islet number 65
Venation 31
Virgin oil 199
Wagner’s reagent 50, 144
Waxes 202
Wilson’s reaction 154
Xanthydrol test 148
Xenia 211
Yondelis 211
Zeatin 86, 110
Zonarol 207
