Docking study of novel antihyperlipidemic thieno[2,3-d]pyrimidine; LM-1554, with some molecular targets related to hyperlipidemia - an investigation into its mechanism of action

Abstract

An investigation into the mechanism of antihyperlipidemic action of 2-chloromethyl-5,6,7,8-tetrahydrobenzo(b)thieno[2,3-d]pyrimidin-4(3H)-one (LM-1554) was carried out through docking experiments with six different molecular targets; Niemann Pick C1 Like1 protein (NPC1L1), ATP citrate lyase (ACL), C-reactive protein (CRP), lanosterol 14α-demethylase (LDM), squalene synthase (SqS) and farnesiod X-receptor (FXR) known to be implicated in the physiology of hyperlipidemia. The interactions of LM-1554 were compared with the interactions of their respective co-crystallized native ligands at the active sites of these receptors. These comparisons are based on their docking parameters, as well as, types of interactions and vicinity with various amino acids in the active site pockets. The interaction of LM-1554 with the target, NPC1L1 has been found to be the quite favourable as compared to those with the other targets assessed in this study.