Docking and QSAR based screening of some naturally occurring diterpenes as inhibitors of angiotensin converting enzyme (ACE) against cardiovascular diseases

Abstract

Background: Many plants have been listed in the traditional systems of medicine and some of these are providing comprehensive relief to the people suffering from cardio-vascular diseases (CVD) and are recognized for their ability to produce secondary metabolites. Secondary metabolites obtained from different plants have been the starting material for designing different drugs. Naturally occurring diterpenes are the secondary metabolites that show myriad varieties of pharmacological activities. These diterpenes exert cardiovascular actions and paved the path towards development of cardioprotective formulations.

Aims and objectives: In the present study we have analyzed the inhibitory potential of naturally occurring diterpenes on the Angiotensin Converting Enzyme (ACE) - the enzyme responsible for various cardiovascular diseases.

Materials and methods: Binding affinity of the diterpenes against known cardioprotective drug target was calculated by performing the docking experiment using FlexX and IC50 values of the compounds were predicted by QSAR analysis.

Results: Toxicity screening revealed that diterpenes were non-toxic and obeyed Lipinski’s rule. The docking studies showed greater affinity of the diterpenes towards the active site of drug target. QSAR analysis revealed significant IC 50 values of the diterpenes.

Conclusion: The study suggests that the diterpenes - Ent-kaur-16-en-15-one-19-oic acid, may be Angiotensin Converting Enzyme targeted potent new drug for treating cardiovascular diseases.

Keywords: Secondary metabolites, diterpenes, ACE, Cardioprotective, IC50