title: Pharmacophore and molecular docking guided 3D-QSAR study of bacterial enoyl-ACP reductase (FabI) Inhibitors.
abstract: Enoyl acyl carrier protein (ACP) reductase (FabI) is a potential target for the development of antibacterial agents. Three-dimensional quantitative structure-activity relationships (3D-QSAR) for substituted formamides series of FabI inhibitors were investigated using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) techniques. Pharmacophore and molecular docking methods were used for construction of the molecular alignments. A training set of 36 compounds was performed to create the 3D-QSAR models and their external predictivity was proven using a test set of 11 compounds. Graphical interpretation of the results revealed important structural features of the formamides related to the active site of FabI. The results may be exploited for further optimization of the design of new potent FabI inhibitors.
authors: Key Laboratory of Regenerative Biology and Institute of Chemical Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, No. 190, Kaiyuan Avenue, Science Park, Guangzhou 510530, China.|Department of Medicinal Chemistry, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China.
authors: Xiaoyun
authors: X
authors: Lu
authors: Key Laboratory of Regenerative Biology and Institute of Chemical Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, No. 190, Kaiyuan Avenue, Science Park, Guangzhou 510530, China.
authors: Man
authors: M
authors: Lv
authors: Department of Medicinal Chemistry, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China.
authors: Kun
authors: K
authors: Huang
authors: Key Laboratory of Regenerative Biology and Institute of Chemical Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, No. 190, Kaiyuan Avenue, Science Park, Guangzhou 510530, China.
authors: Ke
authors: K
authors: Ding
authors: Department of Medicinal Chemistry, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China.
authors: Qidong
authors: Q
authors: You
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry; D019295:Computational Biology; D018360:Crystallography, X-Ray; D030562:Databases, Protein; D024881:Drug Resistance, Bacterial; D050753:Enoyl-(Acyl-Carrier-Protein) Reductase (NADH) / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000737:chemistry; D029968:Escherichia coli Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D054889:Fatty Acid Synthase, Type II / Q000037:antagonists & inhibitors / Q000737:chemistry; D020128:Inhibitory Concentration 50; D008024:Ligands; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D011485:Protein Binding; D021281:Quantitative Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D029968:Escherichia coli Proteins; D008024:Ligands; D050753:Enoyl-(Acyl-Carrier-Protein) Reductase (NADH); C493924:fabI protein, E coli; D054889:Fatty Acid Synthase, Type II