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Abstract

Hyperlipidemia is a term that encompasses various genetic and acquired disorders that describe elevated lipid levels within the human body. The present study aims to design newer potent PCSK9 Inhibitors to treat hyperlipidemia. In the current study, pharmacophoric features like one hydrogen bond acceptor, one hydrogen bond donor, and one aromatic ring were used to construct a virtual library of ligands. A virtual library consists of 150 ligands containing substituted heterocycles like Imidazole, Thiazole, Oxadiazole, thiadiazole, oxazole, Benzthiazole, Amino triazole, Benzoxazole, Pyrimidine, and Pyrrole. The binding mechanism of newly designed ligands with target enzyme PCSK9 was studied using Autodock 4.2.6. Docking studies show that Lig7, Lig15, Lig34, Lig49, and Lig103 were highly active hits, and nearly 90 designed ligands were found to moderately inhibit PCSK9 enzyme, which is proven to be effective hits. When all the 150designed ligands were further subjected to drug-likeliness properties using software like Molinspiration, Osiris property Explorer all ligands were found to possess drug-likeliness properties. INTRODUCTION:Hyperlipidemia is a systemic disease that is characterized by elevated lipid levels in the blood, including total cholesterol (TC), total glyceride (TG), low-density lipoprotein cholesterol (LDL-c), and so on 1 . Hyperlipidemia is classified into a primary and a secondary type, which indicates the complexities associated with the disease. The primary diseases may be treated by using anti-hyperlipidemic drugs, but the secondary originating from diabetes hypothyroidism demands the treatment of the original disease rather than hyperlipidemia 2 .