CoMFA and molecular docking studies of benzoxazoles and benzothiazoles as CYP450 1A1 inhibitors

被引：26

作者：

Pan, Jie ^{[1
]}

Liu, Gen-Yan ^{[1
]}

Cheng, Jin ^{[1
]}

Chen, Xin-Jie ^{[1
]}

Ju, Xiu-Lian ^{[1
]}

机构：

[1] Wuhan Inst Technol, Key Lab Green Chem Proc, Sch Chem Engn & Pharm, Minist Educ, Wuhan 430073, Peoples R China

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2010年 / 45卷 / 03期

关键词：

CYP450; 1A1; CoMFA; Homology modeling; Surflex-docking; CYTOCHROME-P450; ENZYMES; BINDING AFFINITIES; SUBSTRATE-BINDING; HUMAN CYP1A1; P450; HOMOLOGY; METABOLISM; EXPRESSION; PROTEINS; SEQUENCE;

D O I：

10.1016/j.ejmech.2009.11.037

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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(pred)(2) value of 0.809. Furthermore, a three-dimensional model of CYP450 W 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. (C) 2009 Elsevier Masson SAS. All rights reserved.

引用

页码：967 / 972

页数：6

共 29 条

[1] Synthesis and biological properties of benzothiazole, benzoxazole, and chromen-4-one analogues of the potent antitumor agent 2-(3,4-dimethoxyphenyl)-5-fluorobenzothiazole (PMX 610, NSC 721648) [J].

Aiello, Stefania ;

Wells, Geoffrey ;

Stone, Erica L. ;

Kadri, Hachemi ;

Bazzi, Rana ;

Bell, David R. ;

Stevens, Malcolm F. G. ;

Matthews, Charles S. ;

Bradshaw, Tracey D. ;

Westwell, Andrew D. .

JOURNAL OF MEDICINAL CHEMISTRY, 2008, 51 (16) :5135-5139

[2] COMPARATIVE MOLECULAR-FIELD ANALYSIS (COMFA) .1. EFFECT OF SHAPE ON BINDING OF STEROIDS TO CARRIER PROTEINS [J].

CRAMER, RD ;

PATTERSON, DE ;

BUNCE, JD .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1988, 110 (18) :5959-5967

[3]

Ekins S, 2001, DRUG METAB DISPOS, V29, P936

[4] Halloween genes encode P450 enzymes that mediate steroid hormone biosynthesis in Drosophila melanogaster [J].

Gilbert, LI .

MOLECULAR AND CELLULAR ENDOCRINOLOGY, 2004, 215 (1-2) :1-10

[5] Beware of q2! [J].

Golbraikh, A ;

Tropsha, A .

JOURNAL OF MOLECULAR GRAPHICS & MODELLING, 2002, 20 (04) :269-276

[6]

HARDSTONE MC, 2008, J EVOLUTION BIOL, V10, P1420

[7] Human drug metabolising cytochrome P450 enzymes: properties and polymorphisms [J].

Ingelman-Sundberg, M .

NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY, 2004, 369 (01) :89-104

[8] Theoretical quantitative structure-activity relationships of flavone ligands interacting with cytochrome P450 1A1 and 1A2 isozymes [J].

Iori, F ;

da Fonseca, R ;

Ramos, MJ ;

Menziani, MC .

BIOORGANIC & MEDICINAL CHEMISTRY, 2005, 13 (14) :4366-4374

[9] Scoring noncovalent protein-ligand interactions: A continuous differentiable function tuned to compute binding affinities [J].

Jain, AN .

JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN, 1996, 10 (05) :427-440

[10]

Kress S, 1997, CANCER RES, V57, P1264

← 1 2 3 →