statin of fermentation.pptx

statin of fermentation.pptx

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  Presented by: Komal jain M.Pharm Pharmaceutical Chemistry
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   • Introduction • Historyof statins • Mode of action • Production of statins by fermentation • Lovastatin • Simvastatin • Applications CONTENT
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   • The statinsact as competitive inhibitors, specifically inhibiting HMG-CoA reductase, a rate limiting step cholesterol biosynthesis. Statins block the conversion of HMG-CoA reductase to malonic acid in the mevalonate pathway .  Class of statins:  Natural Statins: Lovastatin(mevacor), Compactin, Pravastatin (pravachol), Simvastatin (Zocor).  Synthetic Statins: Atorvastatin (Lipitor),Fluvastatin (Lescol). Introduction
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   History of statins 4 4
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    Lovastatin arenatural statins produced as secondary metabolites by predominantly Aspergillus and Penicillium species.  Lovastatin produced by a fungus, Aspergillus terreus isolated by us from tropical soil. Lovastatin was one of the first cholesterol-lowering drugs.  Simvastatin is obtained a selective enzymatic deacylation of lovastatin.  Many statins are now chemically synthesised but lovastatin is still required to produce simvastatin  From reducing blood cholesterol levels simvastatin causes pleotropic effects and has potential to treat various kinds of disorders including neurodegenerative disease . Lovastatin
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   Mode of action(lovastatin)
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  Production of naturaland semi-synthetic statins by fungi. Simvastatin Pravastatin
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  Fermentation method oflovastatin Wheat bran (40g) as substrate Inoculated with spore suspension (107/8ml spores) of A. terreus . Incubated at 280C for 7 days Culturing of A.terreus by Solid State Fermentation (SSF) 8
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  Inoculated substrate wasdried at 40◦C for 24h Crushed to powder Ethyl acetate (150 ml) was added Filtrate was dried using rotary vacuum evaporator 9
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  One gram ofdried crude lovastatin extract was loaded on to pre-packed silica gel column Elution with benzene (100%), And combination of Benzene: Acetonitrile in the following ratio 95:5, 90:10, 85:15, 80:20 Acetonitrile (100%) Thin Layer Chromatography (TLC) Purification of lovastatin 10
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    Statins alsoreduce hepatic cholesterols leading to reduced gall stone formation and reduced platelet aggregation.  Simvastatin has been found to reduce the incidence of neurodegenerative disorders such as Alzheimer’s disease and Parkinson’s disease.  Lovastatin had proven to reduce the coronary heart diseases (CHD) in the patients, by lowering the plasma cholesterol level.  Lovastatin is reduce proliferation of Lung cancer ,Breast cancer, Liver cancer and cervical cancer. Application
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    Subhan, M.et al. (2016) Exploitation of Aspergillus terreus for the production of natural statins. J Fungi 2, 1–13. doi:10.3390/jof2020013.  Wolozin, B. et al. (2007) Simvastatin is associated with a reduced incidence of dementia and Parkinson’s disease. BMC Med. 5, 20. doi:10.1186/1741-7015-5-20.  Latha, D. Prasanna, KPJ Hema Latha, and D. Sri Rami Reddy. "Production of lovastatin by solid state fermentation by Penicillium funiculosum NCIM 1174."Drug Invention Today 3.6 (2011).  Lee, T. J. H., W. J.; Smith, R. L. Journal of Organic Chemistry 1982, 47, (24), 4750 References