CoMFA and molecular docking studies of benzoxazoles and benzothiazoles as CYP450 1A1 inhibitors.
For better understanding of the molecular interactions of inhibitors with CYP450 1A1, a series of benzoxazoles and benzothiazoles were analyzed by comparative molecular field analysis (CoMFA) and molecular docking. Two conformer-based alignment strategies were employed to construct reliable CoMFA models. The best CoMFA model yielded a predictive correlation coefficient r(2)(pred) value of 0.809. Furthermore, a three-dimensional model of CYP450 1A1 was generated by homology modeling using CYP450 1A2 as a template, and docking of 48 CYP450 1A1 inhibitors into the putative binding sites of the CYP450 1A1 were studied. The results obtained from this study will be helpful in the design of potentially active CYP450 1A1 inhibitors.
Pan
Jie
J
Key Laboratory for Green Chemical Process of Ministry of Education, School of Chemical Engineering and Pharmacy, Wuhan Institute of Technology, Zuodaoquanlu No 366, Hongshan District, Wuhan 430073, People's Republic of China.
Liu
Gen-Yan
GY
Cheng
Jin
J
Chen
Xin-Jie
XJ
Ju
Xiu-Lian
XL
D052160:Benzothiazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001583:Benzoxazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001665:Binding Sites; D003198:Computer Simulation; D019363:Cytochrome P-450 CYP1A1 / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D021281:Quantitative Structure-Activity Relationship; D055672:Static Electricity
D052160:Benzothiazoles; D001583:Benzoxazoles; D004791:Enzyme Inhibitors; D019363:Cytochrome P-450 CYP1A1