title: Identification of dual Acetyl-CoA carboxylases 1 and 2 inhibitors by pharmacophore based virtual screening and molecular docking approach.
abstract: Acetyl-CoA carboxylase (ACC) is a crucial metabolic enzyme that plays a vital role in obesity-induced type 2 diabetes and fatty acid metabolism. To identify dual inhibitors of Acetyl-CoA carboxylase1 and Acetyl-CoA carboxylase2, a pharmacophore modelling approach has been employed. The best HypoGen pharmacophore model for ACC2 inhibitors (Hypo1_ACC2) consists of one hydrogen bond acceptor, one hydrophobic aliphatic and one hydrophobic aromatic feature, whereas the best pharmacophore (Hypo1_ACC1) for ACC1 consists of one additional hydrogen-bond donor (HBD) features. The best pharmacophore hypotheses were validated by various methods such as test set, decoy set and Cat-Scramble methodology. The validated pharmacophore models were used to screen several small-molecule databases, including Specs, NCI, ChemDiv and Natural product databases to identify the potential dual ACC inhibitors. The virtual hits were then subjected to several filters such as estimated [Formula: see text] value, quantitative estimation of drug-likeness and molecular docking analysis. Finally, three novel compounds with diverse scaffolds were selected as potential starting points for the design of novel dual ACC inhibitors.
authors: Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research, Sect-67, SAS Nagar, Punjab 160 062, India.
authors: Anuseema
authors: A
authors: Bhadauriya
authors: Gaurao V
authors: GV
authors: Dhoke
authors: Rahul P
authors: RP
authors: Gangwal
authors: Mangesh V
authors: MV
authors: Damre
authors: Abhay T
authors: AT
authors: Sangamwar
mesh_terms: D000103:Acetyl-CoA Carboxylase / Q000037:antagonists & inhibitors*; D003198:Computer Simulation; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D057927:Hydrophobic and Hydrophilic Interactions; D008956:Models, Chemical; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D009765:Obesity / Q000188:drug therapy*; D013329:Structure-Activity Relationship
chemical_list: D000103:Acetyl-CoA Carboxylase