This document discusses statins, which are a class of drugs that lower cholesterol. It specifically focuses on the natural statins lovastatin and simvastatin. Lovastatin is produced through the fermentation of Aspergillus terreus fungus, while simvastatin is obtained through the enzymatic processing of lovastatin. Both statins work by inhibiting the HMG-CoA reductase enzyme and blocking cholesterol biosynthesis. In addition to lowering cholesterol, statins provide other health benefits such as reduced risk of gallstones, Alzheimer's disease, and cancer proliferation.

1. Presented by:
Komal jain
M. Pharm
Pharmaceutical Chemistry

2. 
• Introduction
• History of statins
• Mode of action
• Production of statins by fermentation
• Lovastatin
• Simvastatin
• Applications
CONTENT

3. 
• The statins act 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

4. 
History of statins
4
4

5. 
 Lovastatin are natural 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

6. 
Mode of action (lovastatin)

7. Production of natural and semi-synthetic statins by fungi.
Simvastatin Pravastatin

8. Fermentation method of lovastatin
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

9. Inoculated substrate was dried at 40◦C for 24h
Crushed to powder
Ethyl acetate (150 ml) was added
Filtrate was dried using rotary vacuum
evaporator
9

10. One gram of dried 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

11. 
 Statins also reduce 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

12. 
 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