Molecular docking of HMG-CoA reductase and inhibitory effect of new derivatives of atorvastatin on this enzyme

Introduction: In the intracellular mevalonate cycle, HMG-CoA reductase catalyzes the conversion of HMGCoAto mevalonate. Mevalonate's metabolic pathway is a very important metabolic pathway in eukaryotesand many bacteria that eventually produce many important compounds such as cholesterol, Isoprenoids andterpenes such as lycopene. All animal cells produce cholesterol at a rate of production that varies in cell typeand organ function. About ۲۰-۲۵% of daily cholesterol production occurs in the stomach, other organs witha higher production rate include the intestines, adrenal glands and reproductive organs. The intracellularsynthesis begins after a acetyl CoA molecule and a aceto acetyl CoA-۱ molecule, which is hydrated to form۳-hydrogen-۳methylglutaryl CoA۱ (HMG-CoA). This molecule is then reduced to mevalonate by the HMGCoAenzyme. This reaction has a slow rate, is a recoverable step in cholesterol synthesis and is the site ofaction for statins.Description: As we know HMG-CoA reductase is inhibited by the statins family drugs. This enzyme,encoded by PDB ID: ۱HWK, via homo saponins taxonomy is inhibited by atorvastatin. This drug inhibitsthis enzyme by blocking the active site of the enzyme and establishing hydrogen and ionic bonds with theamino acids in the active site, eventually reducing cholesterol. The aim of this project was to investigate thenovel derivatives of atorvastatin and the HMG-CoA reductase inhibition.Discussion and conclusion:After drawing the structure of the new atorvastatin derivatives by Marvin Sketchsoftware and examining the amount of energy and its binding to the HMG-CoA reductase enzyme by AutoDock Tools software, it was concluded that the new atorvastatin derivatives also inhibited the enzyme withhigh efficiency and inhibiting the active site of the enzyme, it inhibits it.

کلیدواژه ها:

HMG-CoA ، Atorvastatin ، Auto Dock Tools ، Cholesterol