Molecular docking and ADMET analysis of synthetic statins for HMG-CoA reductase inhibition activity

Toppo, Aditya L ; Yadav, Manisha ; Dhagat, Swasti ; Ayothiraman, Seenivasan ; Jujjavarapu, Satya Eswari

Abstract

Hypercholesterolemia is a serious condition that may lead to coronary heart disease, heart attack and stroke raising the rate of morbidity and mortality in the hypocholesterolemic patients. Statins are one of the largest selling drugs for hypercholesterolemia. They serve as potential competitive inhibitors of HMG-CoA reductase that catalyzes the rate-limiting step of cholesterol biosynthesis cascade. They can be broadly classified into fermentation-derived, semisynthetic and synthetic statins. For the current study, synthetic statins like fluvastatin, cerivastatin, rosuvastatin were subjected to in silico analysis for their competitive binding with HMG-CoA reductase through molecular docking. The molecular interaction between HMG-CoA reductase with statins and their ADMET properties were studied using Maestro suite of Schrödinger software. The results of molecular docking depicted that fluvastatin had the highest docking score while that of rosuvastatin was the least. The prediction of pharmacokinetics of drug performed by QikProp also pointed the efficacy of fluvastatin as a potent inhibitor for HMG-CoA reductase enabling it to be an effective drug to treat hypercholesterolemia among the three synthetic statins.

Keyword(s)

Cerivastatin; Fluvastatin; HMG-CoA reductase; Hypercholesterolemia; Rosuvastatin

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