Download Marine Cyanobacteria Source of Lead Compounds of

Marine Cyanobacteria Source of
Pharmaceutical Important Compounds
MBT Lecture 10
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Cyanobacteria

Cyanobacteria are phylogenetically coherent group of Gramnegative prokaryotes possessing the unifying property of
performing oxygenic plant like photosynthesis with autotrophy as
their dominant mode of nutrition.

Some of the cyanobacterial species can grow in the dark on organic
substrates and others under anaerobic conditions with sulfide as
electron donor for photosynthesis.

Certain strains have the ability to fix atmospheric dinitrogen into
organic nitrogen-containing compounds mainly nitraits.
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
Over 300 nitrogen-containing secondary metabolites have been reported
from the prokaryotic marine cyanobacteria.

A majority of these metabolites are biologically active and are products
of either the nonribosomal polypeptide (NRP) or the mixed polyketideNRP biosynthetic pathways.
Biomolecules of the NRP and hybrid polyketide-NRP structural types are important subsets of
natural products utilized as therapeutic agents.
Polyketides are structurally a very diverse family of natural products with diverse biological activities and
pharmacological properties. They are broadly divided into three classes: type I polyketides
(often macrolides produced by multimodular magasynthases), type II polyketides (often aromatic molecules
produced by the iterative action of dissociated enzymes), and type III polyketides (often small aromatic
molecules
produced
by
fungal
species).
Polyketide
antibiotics,
antifungals,
cytostatics, anticholesteremic, antiparasitic coccidiostates (antiprotozoal agent), animal growth promoters and
natural insecticides are in commercial use

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These include the antibiotic vancomycin, the immuno suppressive agent
cyclosporine like drugs and the anticancer agent.
Sheathed cyanobacterial strains
.
(a) Chroococcus sp. (1000x)
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(b) Phormidium sp. (1000x).
Anticancer Drugs from Marine Cyanobacteria.

Marine cyanobacterial compounds are found to target tubulin or actin
filaments in eukaryotic cells, making them an attractive source of natural
products as anticancer agents. M. A. Jordan and L. Wilson,
“Microtubules and actin filaments: dynamic targets for cancer
chemotherapy,”
Current Opinion in Cell Biology, vol. 10, no. 1, pp. 123–130, 1998.

Prominent molecules such as the antimicrotubule agents, curacin A and
dolastatin 10, have been in preclinical and/or clinical trials as potential
anticancer drug.
Pure curacin A is an antimitotic agent that
inhibits microtubule assembly and the binding of colchicine to tubulin
(proteins that make up microtubules.).

W. H. Gerwick, L. T. Tan, and N. Sitachitta. Alkaloids: Chemistry and Biology,, 2001.

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A synthetic derivative of dolastatin 10 "TZT-1027" was found to be
superior to existing anticancer drugs, such as paclitaxel vincristine
(inhibiting mitosis) is currently undergoing Phase I testing for treating
solid tumors. (Paclitaxel is used to treat against ovarian cancer, breast
cancer, lung cancer and pancreatic cancer)
Anticancer Drugs from Marine Cyanobacteria

Pharmacological studies have also showed the mechanistic novelty of
certain molecules, such as Antillatoxin, in modifying the activity of Nav
channels.

These cyanobacterial toxins are source of valuable molecular tools in
functional characterization of Nav channels as well as potential analgesics
(Pain killler) and neuroprotectants.

Anti-HIV activity of marine cyanobacterial compounds from Lyngbya
lagerheimii and Phormidium tenue.

A massive programme of screening of compound from Cyanobacteria
Resltsin a compound from marine Oscillatoria laete-virians BDU 20801 that
shows anti-Candida activity (anti-fungal infection). An immunopotentiating
compound with male anti-fertility, without being toxic to other systems in a
mice model, was found in the extracts of Oscillatoria willei BDU 130511

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Cyanobacterial Cyclopeptides as Lead
Compounds to Novel Targeted Cancer Drugs

Cyanobacterial cyclopeptides, including microcystins (MC) (hepatotoxic) and
nodularins (Causes bloom in brakish water), are considered a health hazard to
humans due to the possible toxic effects of high consumption.

Microcystins are stable hydrophilic cyclic heptapeptides with a potential to cause
cellular damage following uptake via organic anion transporting polypeptides
(OATPs).

Their intracellular biological effects involve inhibition of catalytic subunits of
protein phosphatase 1 (PP1) and PP2, and glutathione depletion and generation
of reactive oxygen species (ROS.

Certain OATPs are prominently expressed in cancers as compared to normal
tissues, qualifying MC as potential candidates for cancer drug development.

In targeted cancer therapy, cyanotoxins comprise a rich source of natural
cytotoxic compounds with a potential to target cancers expressing specific
uptake transporters
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
These are attractive biological features for the development of potential
anticancer drugs with specific cellular targets.

Apratoxin A (126) is another potent cytotoxic compound worthy of further
biological investigation as anticancer agent due to it mechanism of action in
attenuating the FGF (fibroblast growth factor) signaling pathway.
FGF are a family of growth factors, with members involved
in angiogenesis, wound healing, embryonic development and various endocrine
signaling pathways.


Synthetic analogues based on the scaffolds of these cyanobacterial natural
products can be developed for SAR (structure activity relationship) studies as
well as lead optimization for drug development

Medically important gamma linolenic acid (GLA) is relatively rich in
cyanobacteria Spirulina platensis and Arthrospira sp. which is easily converted into
arachidonic acid in the human body and arachidonic acid into prostaglandin E2

Prostaglandin E2 has lowering action on blood pressure and the contracting
function of smooth muscle and thus plays an important role in lipid metabolism
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Vitamins and enzymes from Cyanobacteria

Cyanobacteria being photoautotrophs have the abilityto photosynthetically transform
simple, labelled compounds such as into complex organic compounds. Isotopically
labelled cyanobacterial metabolites such as sugars, lipids and amino acids are
commercially available

Some of the marine cyanobacteria appear to be potential sources for large-scale
production of vitamins of commercial interest such as vitamins of the B complex
group and vitamin E.

The carotenoids and phycobiliprotein pigments of cyanobacteria have commercial
value as natural food colouring agents, as feed additives, as enhancers of the color of
egg yolks, to improve the health and fertility of cattle, as drugs, and in the cosmetic
industries.

Cyanobacteria secrete enzymes that can be exploited commercially. Marine
cyanobacteria have been used in large-scale production of enzymes such as beta
lactamase, protease and lipas . They also secrete cytein and serine protease inhibitor.

These products can be marketed at low cost since relative biomass production of
cyanobacteriais much less expensive than bacteria.
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Potential Commercial Development of Insecticides, Algaecides, and
Herbicides from Cyanobacteria

Potential commercial development of cyanobacterial compounds for
nonbiomedical applications, particularly include herbicides, algaecides, and
insecticides

Fladmark et al. screened extracts from 76 isolates of cyanobacteria and found
several of these isolates produced compounds that were larvicidal to Aedes aegypti.

The greatest inhibition, however, was associated with presence of the hepatotoxic
microcystins and the neurotoxic anatoxin-a.

Methanolic extracts from an isolate of Westiellopsis sp. were larvicidal to several species
of mosquito, including representatives of Aedes aegypti (a vector forDengue Fever),
Anopheles stephensi (a vector for malaria), and Culex tritaeniorhynchus and C.
quinquefasciatus (vectors of encephalitis).

The use of genetically engineered cyanobacteria, specifically expressing the
insecticidal proteins from Bacillus thuringiensis to control mosquito larvae is also in
use.
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Biofertilizers

Since most species are nitrogen fixing and several of them are soil dwelling,
making them an ideal biofertilizers.

Inherent fertility of tropical rice field soils depend on the activity of N2-fixing
cyanobacteria. A variety of cyano-bacterial strains colonize rice fields wherein
heterocystous species are capable of fixing atmospheric nitrogen.

However, several non-heterocystous cyanobacteria are able to fix atmospheric
nitrogen under microaerophilic (very low oxygen requirement: 2-10%)
conditions.

In situ estimations using acetylene reduction technique have shown an addition
of 18–15 kg N ha– yr–1 due to the activity of diazotrophic cyanobacteria.

The role of N2 –fixing cyanobacteria in maintenance of the fertility of rice fields
has been well substantiated and documented all over the world. In India alone,
the beneficial effects of cyanobacteriaon yield of many rice varieties have been
demonstrated in a number of field locations
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Biofertilizers

Beneficial effects of cyano-bacterial inoculation have also been
reported on a numbe rof other crops such as barley, oats,
tomato, radish, cotton,sugarcane, maize, chilli and lettuce

The cyano-bacterial symbiont Anabaena-azollae fixes atmospheric
nitrogen estimated between 120 and 312 kg N2 per hectare.

Azolla supplies 150–300 tons per hectare per year of green manure,
which supports growth of soil microorganisms including
heterotrophic N2 fixers
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Cyanobacteria in waste treatment

Use of Cyanobacteria in waste treatment is beneficial in different ways since
they can bring about oxygenation and mineralization, in addition to serving
asfood source for aquatic species.

Using the marine cyano-bacteria Oscillatoria sp. BDU 10742, Aphanocapsa sp.
BDU 16 and a halophilic bacterium Halobacterium US 101, Uma and
Subramanian et al., 1997 treated ossein factory effluent which resulted in
reduced calcium and chloride levels and enabled 100% survival and
multiplication of Tilapia fish with only cyanobacteria as feed source.

Phormidium valderianum BDU 30501 was able to tolerate and grow at a phenol
concentration of 50 mg/l and removed 38 mg/l within a retention period of
sevendays.

This result opens up the possibility of treating a variety of phenol containing
effluents. The organism was also effective in optimal sorption/desorption of
heavy metal ions (Cd2+,Co2+)
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