Cyanobacteria are prokaryotic oxygenic phototrophs found in almost every conceivable habitat on earth. This presentation briefly describes applications of cyanobacteria in pharmaceutical industry.
2. INTRODUCTION
• Prokaryotic oxygenic phototrophs
• Found in almost every conceivable habitat on earth.
• Oldest prokaryotic organism evolved over two billions years ago.
• Belongs to monophyletic group
• Responsible for accumulating atmospheric oxygen and photosynthetic
capacity of plants
Ferris et al. 1996; Ward et al. 1997; Nübel et al. 1999, 2000;
Abed and Garcia‐pichel 2001
Cyanobacteria
3. • Richard E. Moore popularized cyanobactetria derived natural products
during 1970, in collaboration with William H. Gerwick during the late
1980 . The result from their research proved that cyanobacteria are
prolific sources of bioactive and chemically diverse secondary metabolites.
• Nearly 58% of cyanobacterial metabolites have been produced by
Ocillatoriales
• 35% production is mainly from Lyngbya genus
• the marine Lyngbya lineage is the most prolific source of cyanobacterial
metabolites.
CYANOBACTERIAL
SECONDARY
METABOLITE
Non- toxic secondary
metabolite(phytohormones,
sidephore, UV-protective
compound
Toxic secondary metabolite
(Hepatoxin,
Neurotoxin,Dermatotoxin,
Cytotoxin)
APPLICATIONS
Biocides
Chelators
Biofertilizers
Biofules and
bioremediation
Pharnaceuticals
Cosmetics
4. CONCLUSION
Cyanobacteria constitute a unique group of oxygenic photosynthetic bacteria and
populate diverse habitats throughout the world.
Cyanobacteria are one of the richest sources of known and novel bioactive compounds
including toxins with wide pharmaceutical applications is unquestionable.
Their potential as a good source of new therapeutic lead compounds has been realized
during the past two decades, as several bioactive molecules obtained from cyanobacteria
show a broad spectrum of activities, such as antitumor, antibacterial, and antiviral
effects, and protease inhibition cyanobacterial secondary metabolites may constitute a
prolific source of new entities leading to the development of new pharmaceuticals.
Currently, several potent molecules, such as largazole, apratoxins, symplostatin and , are
identified as drug leads in various disease areas, particularly in cancer treatment.
Hence, pharmaceutical potential of cyanobacteria deserves more scientific attention and
interdisciplinary research, and cyanobacterial strains from still unexplored and extreme
habitats can serve as good.
5. Cyanobacterial metabolites shows exciting
pharmaceuticals applications
Pharmaceutical
applications of
cynobacterial
Anti-
microbial
Anti-HIV
Anti-
cancer
Anti-
viral
Anti-
fungal
Anti-
bacterial
Immuno-
suppressant
Gademann K et al. (2008) ,
Wase NV et al. (2008),
Mayer AMS et al. (2005)
6. • Main focus is given on the search of drugs for dreadful human
diseases such as cancer and AIDS.
• Bioactive molecules like curacin a, largazole and apratoxin
succeeded in reaching into phase II and phase III clinical trials.
• These metabolites interfere with specific cellular targets, such
as tubulin, actin, and histone deacetylases, making them an
attractive source of natural products for drug discovery.
7. S.No.
BIOACTIVE
COMPOUND SPECIES FUNCTION MECHANISMS OF ACTION REFERENCES
1 Dolastatin Dolabella
auricularia
Breast cancers
Binds to tubulin on the rhizoxin-binding
site and affects microtubule assembly
arresting the cell into G2/M phase.
Natsume et al.
(2003)
Kobayashi et al.
(1997)
2 Largazole Symploca sp.
Antiproliferative activity,
breast cancer and
colorectal carcinoma
Inhibits Class I histone deacetylases
(HDACs).
Luesch et al.
(2001)
3 Aurilide Dolabella
auricularia
H-460 lung tumor
Potent inhibitor of mitochondrial
prohibitin 1. The inhibition of prohibitin 1
resulted in the activation of the proteolytic
process of optic atrophy 1, which further
led to mitochondria- induced apoptosis.
Sato et al. (2011)
Pei et al. (2012)
4 Apratoxin A
Lyngbya
majuscula
Osteosarcoma, HT29 colon
adenocarcinoma, and
HeLa cervical carcinoma
Inducing G1-phase cell cycle arrest and
apoptosis.
Grinberg et al .
(2002)
ANTICANCEROUS DRUGS
8. S.NO.
BIOACTIVE
COMPOUND
SPECIES FUNCTION MECHANISMS OF ACTION REFERENCE
5 Coibamide A
Leptolyngby
a sp.
Cytotoxicity
against NCI-H460
lung and mouse
neuro-2a cells
Inhibit tubule assembly and arrest
cell cycle
Medina et al.
(2008)
6 Curacin A
Lyngbya
majuscula
Breast cancer Inhibits cross-linking of tubulin.
Klasse et al. (2008)
Xiong et al. (2006)
7 Hoiamide A
L. majuscule
and
Phormidium
gracile
H-460 lung cancer
Inhibits (3H) batracho-toxin
binding to voltage- gated sodium
channels (VGSCs
Cao et al . (2015)
8 Bisebromoamide Lyngbya sp.
HeLa S3 epithelial
carcinoma
Inhibited phosphorylation
of extracellular signal-regulated
kinase and AKT (protein
kinase)
Li et al. (2011)
Teruya et al. (2009)
9. ANTI-HIV DRUGS
The following are the three classes of cyanobacterial compounds with potent in
vitro antiviral activity:
Anti-HIV
Compound
Spirulan
and
Ca-spirulan
Nostoflan
Carbohydrate-
binding proteins,
cyanovirin-N and
scytovirin,
10. 1) Spirulan and ca-spirulan
• Isolated from spirulina sp.,
• Show potent and broad-spectrum activity against HIV-1, HIV-2, H1 influenza,
• Inhibit the reverse transcriptase activity of HIV-1,
• Inhibit the fusion between HIV-infected and HIV-uninfected CD4+ lymphocytes.
2) Nostoflan
• An acidic polysaccharide from nostoc flagelliforme,
• Exhibits potent virucidal activity against herpes simplex virus.
3) Cyanovirin-N and Scytovirin
• Two carbohydrate-binding proteins,
• Shows antiviral activity by interfering with multiple steps in the viral fusion process.
Sielaff H et. al(2006)
11. 3.2 Scytovirin
• It is a 95-amino-acid-long.
• 9.7 kDa polypeptide containing five intra-chain disulphide bonds.
• Binds to the envelope glycoprotein of HIV (gp120, gp160, and gp41) and inactivates the virus
3.1 Cyanovirin-N
• It is a 101-amino-acid-long.
• 11 kDa polypeptide isolated from Nostoc ellipsosporum
• It interferes with the binding of HIV gp120 proteins with CD4+ receptors and thus, inhibits
fusion of HIV virus with CD4+ cell membrane.
12. Neuropharmacological Agents: Sodium Channel Modulators
• Marine cyanobacterial also possess potent neurotoxic properties.
• Majority of these neurotoxins appear to either activate (e.g. antillatoxin) or
block (e.g. kalkitoxin and jamaicamide) mammalian voltage-gated sodium
channels (VGSCs).
• VGSCs are transmembrane ion channels found on neuron and muscle cells and
are involved in rapid electrical signalling via influx of sodium ions.
• Chemical ligands interacting with VGSCs, particularly as blockers, are potential
treatments of various neurological disorders, including cardiac arrhythmias,
epilepsy, neurodegenerative diseases and neuropathic pain.
13. Marine cyanobacteria are known to be a prolific source of many cyclic
and linear depsipeptides having potent protease inhibitory properties.
Proteases are involved in many signaling pathways and they represent
potential drug targets for the treatment of various diseases, including
cardiovascular disorders, cancer and parasitic and viral infections.
Eg. Tasiamide B
statin-containing depsipeptide
inhibit the aspartic protease b-site amyloid precursor protein (APP)
cleaving enzyme type 1 (BACE1)
BACE1, also known as b-secretase, is involved in the abnormal
production of b-amyloid plaques in Alzheimer’s disease BACE1 is
therefore a potential drug target.
Protease inhibitors
