COMPUTER-AIDED MOLECULAR DESIGN OF NOVEL HMG-CoA REDUCTASE INHIBITORS FOR THE TREATMENT OF HYPERCHOLESTEROLEMIA

Abstract

Elevated cholesterol levels are a primary risk factor for the development of coronary artery disease. Dietary changes associated with drug therapy can reduce high serum cholesterol levels and dramatically decrease the risk of stroke and overall mortality. HMG- CoA reductase is an important molecular target of hypolipemic drugs, known as statins, which are effective in the reduction of cholesterol serum levels, attenuating cholesterol synthesis in-liver by competitive inhibition regarding the substrate HMG- CoA . In this paper, we have focused on computer-aided molecular design using density functional theory, flexible docking, molecular dynamics as well as ADME, and synthetic accessibility analyses in order to propose novel potential HMG- CoA reductase inhibitors, designed by bioisosteric modifications which are promising for the treatment of hypercholesterolemia.