title: 3D-QSAR and docking studies of flavonoids as potent Escherichia coli inhibitors.
abstract: Flavonoids are potential antibacterial agents. However, key substituents and mechanism for their antibacterial activity have not been fully investigated. The quantitative structure-activity relationship (QSAR) and molecular docking of flavonoids relating to potent anti-Escherichia coli agents were investigated. Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were developed by using the pIC50 values of flavonoids. The cross-validated coefficient (q(2)) values for CoMFA (0.743) and for CoMSIA (0.708) were achieved, illustrating high predictive capabilities. Selected descriptors for the CoMFA model were ClogP (logarithm of the octanol/water partition coefficient), steric and electrostatic fields, while, ClogP, electrostatic and hydrogen bond donor fields were used for the CoMSIA model. Molecular docking results confirmed that half of the tested flavonoids inhibited DNA gyrase B (GyrB) by interacting with adenosine-triphosphate (ATP) pocket in a same orientation. Polymethoxyl flavones, flavonoid glycosides, isoflavonoids changed their orientation, resulting in a decrease of inhibitory activity. Moreover, docking results showed that 3-hydroxyl, 5-hydroxyl, 7-hydroxyl and 4-carbonyl groups were found to be crucial active substituents of flavonoids by interacting with key residues of GyrB, which were in agreement with the QSAR study results. These results provide valuable information for structure requirements of flavonoids as antibacterial agents.
authors.affiliation: Key Laboratory of Environment Correlative Dietology (Huazhong Agricultural University), Ministry of Education, Wuhan 430070, P.R. China.
authors.forename: Yajing
authors.initials: Y
authors.lastname: Fang
authors.affiliation: Agricultural Bioinformatics Key Laboratory of Hubei Province, College of Informatics, Huazhong Agricultural University, Wuhan 430070, P.R. China.
authors.forename: Yulin
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Oilcrops Research Institute, Chinese Academy of Agricultural Sciences, Wuhan 430062, P.R. China.
authors.forename: Xixi
authors.initials: X
authors.lastname: Zang
authors.affiliation: Key Laboratory of Environment Correlative Dietology (Huazhong Agricultural University), Ministry of Education, Wuhan 430070, P.R. China.
authors.forename: Ting
authors.initials: T
authors.lastname: Wu
authors.affiliation: College of Science, Huazhong Agricultural University, Wuhan 430070, P.R. China.
authors.forename: XiaoJuan
authors.initials: X
authors.lastname: Qi
authors.affiliation: Key Laboratory of Environment Correlative Dietology (Huazhong Agricultural University), Ministry of Education, Wuhan 430070, P.R. China.
authors.forename: Siyi
authors.initials: S
authors.lastname: Pan
authors.affiliation: Key Laboratory of Environment Correlative Dietology (Huazhong Agricultural University), Ministry of Education, Wuhan 430070, P.R. China.
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Xu
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology; D027081:DNA Gyrase / Q000737:chemistry / Q000378:metabolism*; D004926:Escherichia coli / Q000187:drug effects* / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000378:metabolism; D005419:Flavonoids / Q000737:chemistry* / Q000494:pharmacology*; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D021281:Quantitative Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D029968:Escherichia coli Proteins; D005419:Flavonoids; D000255:Adenosine Triphosphate; D027081:DNA Gyrase