IN-SILICO IDENTIFICATION OF NEWER POTENTIAL PROPROTEIN CONVERTASE SUBSTILSIN/KEXIN TYPE 9 INHIBITORS AS POTENT ANTI-HYPERLIPIDEMIC AGENTS
AbstractHyperlipidemia 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.
Article Information
40
5152-5168
2041 KB
297
English
IJPSR
R. Priyadarsini * and V. Dinesh Kumar
Department of Pharmaceutical Chemistry, College of Pharmacy, Madras Medical College, Park Town, Chennai, Tamil Nadu, India.
rpdharsinimpharam@gmail.com
18 April 2022
26 May 2022
18 June 2022
10.13040/IJPSR.0975-8232.13(12).5152-68
01 December 2022
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