3D-pharmacophores of flavonoid binding at the benzodiazepine GABAA receptor site using 4D-QSAR analysis

被引：45

作者：

Hong, X ^{[1
]}

Hopfinger, AJ ^{[1
]}

机构：

[1] Univ Illinois, Coll Pharm, Lab Mol Modeling & Design MC 781, Chicago, IL 60612 USA

来源：

JOURNAL OF CHEMICAL INFORMATION AND COMPUTER SCIENCES | 2003年 / 43卷 / 01期

关键词：

D O I：

10.1021/ci0200321

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

4D-QSAR analysis was applied to a training set of 38 flavonoids where affinity constants, Ki, to the GABA(A) benzodiazepine receptor site, BzR, were determined. It was found that the -logKi values of the compounds are highly dependent on the size and electrostatics character of the substituents at the R-3' and R-6 positions of the flavonoid scaffold. Polar negative groups correctly embedded in the R-3' and/or R-6 suhstituents are predicted to increase -logKi values. A planar conformation of the flavonoid scaffold was found not to be a requirement for the flavonoids to be active. A test set of four compounds was used to evaluate the predictivity of the 4D-QSAR models.

引用

页码：324 / 336

页数：13

共 34 条

[1] Four-dimensional quantitative structure-activity relationship analysis of a series of interphenylene 7-oxabicycloheptane oxazole thromboxane A2 receptor antagonists [J].

Albuquerque, MG ;

Hopfinger, AJ ;

Barreiro, EJ ;

de Alencastro, RB .

JOURNAL OF CHEMICAL INFORMATION AND COMPUTER SCIENCES, 1998, 38 (05) :925-938

[2] CONFORMATIONAL-ANALYSIS .130. MM2 - HYDROCARBON FORCE-FIELD UTILIZING V1 AND V2 TORSIONAL TERMS [J].

ALLINGER, NL .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1977, 99 (25) :8127-8134

[3]

*CHEM21 GROUP INC, 1997, 4D QSAR US MAN VERS

[4] Structure-activity relationships and molecular modeling analysis of flavonoids binding to the benzodiazepine site of the rat brain GABAA receptor complex [J].

Dekermendjian, K ;

Kahnberg, P ;

Witt, MR ;

Sterner, O ;

Nielsen, M ;

Liljefors, T .

JOURNAL OF MEDICINAL CHEMISTRY, 1999, 42 (21) :4343-4350

[5]

DOHERTY DC, 1997, MOLSIM USERS GUIDE

[6]

Dunn III W. J., 1989, TETRAHEDRON COMPUT M, V2, P349, DOI DOI 10.1016/0898-5529(89)90004-3

[7]

Friedman J., 1988, 102 STANF U DEP STAT

[8]

HABERLEIN H, 1994, PHARMAZIE, V49, P912

[9] Construction of a virtual nigh throughput screen by 4D-QSAR analysis:: Application to a combinatorial library of glucose inhibitors of glycogen phosphorylase b [J].

Hopfinger, AJ ;

Reaka, A ;

Venkatarangan, P ;

Duca, JS ;

Wang, S .

JOURNAL OF CHEMICAL INFORMATION AND COMPUTER SCIENCES, 1999, 39 (06) :1151-1160

[10] Construction of 3D-QSAR models using the 4D-QSAR analysis formalism [J].

Hopfinger, AJ ;

Wang, S ;

Tokarski, JS ;

Jin, BQ ;

Albuquerque, M ;

Madhav, PJ ;

Duraiswami, C .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1997, 119 (43) :10509-10524

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