LD50 681 (mg/kg, in mice), Actinopy

LD50 681 (mg/kg, in mice), Actinopyga mauritiana
collected from Lakshadweep in October showed hypotensive and antimicrobial
activities LD50 215 (mg/kg, in mice), and Thelenata ananas collected from
Lakshadweep showed antimicrobial activity, LD50 56.2 (mg/kg, in mice).
The extracts of Holothuria ichinitis collected from Mandapam, Tamilnadu,
in April and H. impotium collected from Lakashadweep in April were found
toxic, LD50 26.1 and 38.3 (mg/kg, in mice) respectively. The species of
Mollusca which showed activity are : Nerita spp. collected from Mandapam,116 Bioactive Marine Natural Products
Tamilnadu, in January showed CNS stimulant activity, LD50 68.1 (mg/kg, in
mice); Octopus vulgaris collected from Okha, Gujarat, in December exhibited
spasmolytic activity, LD50 1000 (mg/kg, in mice) and Onchidium verruculatum
collected from Mandapam, Tamilnadu, in May showed hypoglycaemic activity,
LD50 more than 1000 (mg/kg, in mice). The ability of Octopi to paralyse
prey before ingestion, with secretions of posterior salivary glands has long
been known. The active agents present in the salivary glands of the Octopus
have been found to be a mixture of low molecular weight amines, peptides,
and proteinaceous materials.87 Ghiretti et al88 isolated an active proteinaceous
fraction from the salivary glands of Octopus valgaris and O. macropus.
While these authors found that the toxins from Octopi have paralytic and
hypotension action, the investigations on Octopus vulgaris indicated only
spasmolytic action.
Forty marine invertebrates belonging to the Mollusca, Coelentrata,
Echinodermata and Porifera have been tested for antibacterial, antifungal,
antiamoebic, antimalarial, antiviral, antifertility, hypoglycaemic and a wide
range of pharmacological activities. Of these, three extracts each exhibited
antiimplantation and hypoglycaemic activities; four were found toxic, five
had antiviral activity against EMCV and or RDV, seven gave evidence of
hypotensive activity, while nine extracts were found to be diuretic. One
extract had the CNS stimulant effect, and one had oxytoxic activity as well
as low order of abortifacient activity. Besides eight extracts revealed more
than one type of activity.89 The species of Coelenterata which showed activity
are: Acropora corymbosa collected from Kadmai Island, Lakshadweep, in
January showed CVS activity, Acropora formica collected from the same
locality showed diuretic activity, LD50 2.15 (mg/kg, in mice), Acropora humilis
collected from the Kadmai Island, Lakshadweep, in January exhibited antiviral
activity against Ranikhet Disease virus, LD50 more than 1000 (mg/kg, in
mice), Alcyonaria spp. collected from the same locality exhibited diuretic,
and hypoglycaemic, activities, LD50 3.16 (mg/kg, in mice); Montipora
divaricata collected from Krusadai Island, Tamilnadu, in September showed
hypoglycaemic activity, LD50 1000 (mg/kg, in mice), Paracondylacts spp.
collected from Chandipur, Orissa, in April showed antiimplantation activity
in rats, LD50 more than 1000 (mg/kg in mice); Zoanthus spp. collected from
Veraval, Gujarat, in April showed cardiovascular effects. The species of
Crustacean which showed activity is Eurythoe complanata collected from
Chandipur in April showed diuretic activity. The species of Echinodermata
which showed activity are: Pentaceraster regulus collected from Rameswarm,
Tamilnadu, in September showed diuretic and antiviral activity against
Encephalomyocaritis virus; Ischnochiton campus collected from Orissa in
March exhibited antiimplantation activity in rats and CNS activity, LD50
26.1 (mg/kg, in mice); Modiolus striatulus collected from Krishnapuram,
Orissa in February showed diuretic activity, Terebralia palustris, collected
from South Andaman in April showed cardiovascular effects. The species ofBioactivity of Marine Organisms 117
Porifera which showed activity are: Axinella andamanensis collected from
the Red Skin island, South Andaman, in April showed cardiovascular activity,
LD50 46.4 (mg/kg, in mice), Callyspongia spinosissima collected from
Rameswaram, Tamilnadu, in September showed antiviral activity against
Ranikhet Disease virus and Encephalomyocarditis virus; Heteronema erecta
from Red Skin island, South Andaman in September exhibited hypoglycaemic
activity, Sigmadocia pumlla from Rameswaram, Tamilnadu, in September
showed, diuretic, antiimplantation activity in rats and cardiovascular effect;
Spirastrella inconstans from Krusadai island, Tamilnadu, in September
exhibited diuretic activity, LD50 more than 1000 (mg/kg, in mice and
Spirastrella inconstans var. digitata from Rameswarm, Tamilnadu, in
September showed antiviral activity against Encephalomyocarditis virus.
Many Coelenterates produce toxins or other biologically active metabolites
not only for self-defence but at times to capture prey. Echinoderms are
known to contain polyhydroxysteroids and saponins. Most of these saponins
are reported to have haemolytic activity. Mostly the secondary metabolites
isolated from hard crust Molluscs are venomous in nature, and are used by
the animals to capture prey. Sponges are by far the most extensively studied
marine animals. A variety of biologically active constituents have been isolated
from sponges.
Extracts of marine organisms have been assayed for their cardiovascular90
and toxic properties.91 The results of screening of 118 marine organisms
(Coral, Alcyoniarians, Molluscs, Echinoderms) found in coastal waters of
India, for their toxicity on fish and mice fingerlings as well as their hemolytic
activities are reported.92Echinoderms were found to be toxic to both fish and
mice. They also exhibited high order of hemolytic activity. The Alcyoniarians
were found toxic to fish and mice, but had weak hemolytic activity. The
Molluscs, Patelia chathalamus, Trochus spp., Conus spp., Siganus spp. and
Conus textile were found toxic to fish only, whereas Drupa heptogonalis was
found lethal only to mice. The coral Acropora formosa and A. millepora
exhibited hemolytic activity and were the only corals toxic to mice. Subergorgia
suberosa, the only gorgonian collected showed lethal toxicity to fish as well
as strong hemolytic activity. The sponges did not show toxic reaction to fish
and mice, but exhibited weak hemolytic activity. Specimen of Spirastrella
inconstans, Porites lutea, Pocillopora damicornis, Favites abdita, Montipora
digitata and Noditittoria pyramidalis, collected from three different locations
to determine whether their biotoxicity differs with change in ecological
conditions, showed that their biotoxicities did not differ with ecological
changes.
4.4 Search of Pharmaceutically Useful Compounds
Rinehert et al93 have been searching pharmaceutically useful compounds
from marine organisms. Their first effort invovled a survey of marine organisms
for antibacterial and antifungal properties. The bioassay were carried out on118 Bioactive Marine Natural Products
shipboard.94 These were the first systematic shipboard assay for pharmaceutical
activity, and had many advantages.95,96 The most active antiviral extract in
shipboard testing was from a tunicate identified as Eudistoma olivaceum,
97
but the extract was surprisingly inactive in the secondary assay. However, the
extract of the recollected sample proved very active in both primary and
secondary assays against Herpes simplex and other viruses, confirming the
value of on site assay. Chemical investigation of the bioactive extract of
Eudistoma yielded 17 eudistomins having variously substituted β-
carbolines.98,99 Although all the isolated compounds exhibited antimicrobial
or antiviral activity, the most potent compounds were the tetracyclic eudistomins
with the unique oxathiazepine ring. The in vivo testing of these compounds
could not be carried out due to the scarcity of the tunicate and paucity of
many of the eudistomins. Rinehart et al100,101 have synthesised a number of
these eudistomins. However, oxathiazepine eudistomins have been prepared
in extremely poor yield.
The extract of the tunicate Trididemnum solidum was found to have potent
antiviral activity in bioassays carried out on shipboard.93 It was also found to
be most cytotoxic. Moreover, these activities were confirmed in in vivo
testing at Upjohn,101 USA. Nine major and several minor didemnins have
been isolated from the extract of T. solidum102-104 which is widely distributed
and didemnin-B was relatively abundant in it. Syntheses of some didemnins
have been reported.105,106 Didemnins are active in vivo against DNA and
RNA viruses. Of these, didemnin-B is the most active. Besides, didemnin-B
exhibits remarkable immunosuppressant activity.107 It is 1000 times as potent
as cyclosporin-A in inhibiting T-cell mitogenesis. It has also been shown in
vivo activity in prolonging skin grafts.96 Unfortunately, didemnin-B is toxic.
Ecteinascidia turbinata is reported to contain a potent antitumour agent.108
An interesting immunoregulatory activity was subsequently observed in the
extract of the organism.109 Later on, cytotoxicity was found in the extract.
Counter current chromatography and TLC bioautography on tissue culture
plates resulted in the isolation of ecteinascidins in yields 10-4 to 10-6 percent.96
All the compounds had either anti-bacterial activity or cytotoxicity against L
1210 leukemia cells.96
Over 300 marine organisms from Okinawan water have been screened for
cytotoxicity, antiviral and antimicrobial activities.110 An extract of a sponge
Theonella spp. was found highly cytotoxic in the assay against P 388 murine
leukemia cells. Bioassay guided separation led to the isolation of an active
constituent designated as misakinolide A, which had IC50 10 ng/ml in in
vitro tests and T/C 145% at a dose of 0.5 mg/kg against P 388 in mice. The
biology and ecology of tropical Holothurians have been reviewed.111 Work
has been conducted on the toxicity of sponges and holothurians.112
5. Actinomycetes
Actinomycetes play a major role in producing antibiotic