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.
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.
Department of Pharmaceutical Chemistry, Bombay College of Pharmacy, Mumbai, 400 098 Maharashtra India.
Vijay M
VM
Khedkar
Department of Pharmaceutical Chemistry, Sinhgad Institute of Pharmaceutical Sciences, Lonavala, Pune, 410 401 Maharashtra India ; Department of Chemistry, Banasthali University, Tonk, 304 022 Rajasthan India.
Nikhilesh
N
Arya
Department of Pharmaceutical Chemistry, Bombay College of Pharmacy, Mumbai, 400 098 Maharashtra India.
Evans C
EC
Coutinho
B.V. Patel Pharmaceutical Education and Research Development (PERD) Centre, S.G. Highway, Thaltej, Ahmedabad, 380 054 Gujarat India.
Chamanlal J
CJ
Shishoo
Department of Pharmaceutical Chemistry, Sinhgad Institute of Pharmaceutical Sciences, Lonavala, Pune, 410 401 Maharashtra India.
Kishor S
KS
Jain
2-chloromethylthieno[2,3-d]pyrimidine; Antihyperlipidemic; Docking experiments; LM-1554; Molecular targets