title: 3D-QSAR studies on malonyl coenzyme A decarboxylase inhibitors.
abstract: Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were performed on a series of Malonyl Co-A decarboxylase (MCD) inhibitors (Cheng et al. J. Med. Chem.2006, 49, 1517-1525 and Cheng et al. Bioorg. Med. Chem. Lett.2006, 16, 695-700). These inhibitors have shown protective action on the ischemic heart by inhibiting fatty acid oxidation. The CoMFA model produced statistically significant results, with the cross-validated and conventional correlation coefficients being 0.544 and 0.986, respectively. The best results were obtained by combining steric, electrostatic, hydrophobic, and H-bond acceptor fields in CoMSIA, in which case the respective cross-validated and conventional correlation coefficients were 0.551 and 0.918. The predictive ability of CoMFA and CoMSIA, determined using a test set of 24 compounds, gave predictive correlation coefficients of 0.718 and 0.725, respectively. The information obtained from CoMFA and CoMSIA 3D contour maps may be of utility in the design of more potent MCD inhibitors.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy & Allied Health Professions, St. John's University, Jamaica, NY 11439, USA.
authors.forename: Maulik R
authors.initials: MR
authors.lastname: Patel
authors.forename: Tanaji T
authors.initials: TT
authors.lastname: Talele
mesh_terms: D000465:Algorithms; D002262:Carboxy-Lyases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006860:Hydrogen Bonding; D007202:Indicators and Reagents; D008958:Models, Molecular; D021281:Quantitative Structure-Activity Relationship; D015203:Reproducibility of Results
chemical_list: D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D002262:Carboxy-Lyases; C021532:malonyl-CoA decarboxylase