Open Access3D-QSAR and docking studies of flavonoids as potent Escherichia coli inhibitors
Author(s) -
Yajing Fang,
Yulin Lu,
Xixi Zang,
Ting Wu,
Xiaojuan Qi,
Siyi Pan,
Xiaoyun Xu
Publication year - 2016
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/srep23634
Subject(s) - chemistry , quantitative structure–activity relationship , stereochemistry , docking (animal) , steric effects , dna gyrase , flavones , hydrogen bond , partition coefficient , combinatorial chemistry , escherichia coli , biochemistry , molecule , organic chemistry , medicine , nursing , chromatography , gene
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 pIC 50 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.