Molecular docking and QSAR study on steroidal compounds as aromatase inhibitors

被引：50

作者：

Dai, Yujie ^{[1
]}

Wang, Qiang

Zhang, Xiuli ^{[2
]}

Jia, Shiru

Zheng, Heng ^{[3
]}

Feng, Dacheng ^{[4
]}

Yu, Peng

机构：

[1] Tianjin Univ Sci & Technol, Coll Bioengn, TEDA, Minist Educ,Key Lab Ind Microbiol, Tianjin 300457, Peoples R China

[2] Univ Missouri, Dept Biochem, Columbia, MO 65211 USA

[3] China Pharmaceut Univ, Sch Life Sci & Technol, Nanjing 210009, Peoples R China

[4] Shandong Univ, Coll Chem & Chem Engn, Jinan 250100, Peoples R China

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2010年 / 45卷 / 12期

关键词：

Molecular docking; QSAR; Steroidal compound; Aromatase inhibitor; RECEPTOR MODULATORS SERMS; BINDING; DESIGN;

D O I：

10.1016/j.ejmech.2010.09.011

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

In order to develop more potent, selective and less toxic steroidal aromatase (AR) inhibitors, molecular docking, 2D and 3D hybrid quantitative structure activity relationship (QSAR) study have been conducted using topological, molecular shape, spatial, structural and thermodynamic descriptors on 32 steroidal compounds. The molecular docking study shows that one or more hydrogen bonds with MET374 are one of the essential requirements for the optimum binding of ligands. The QSAR model obtained indicates that the aromatase inhibitory activity can be enhanced by increasing SIC, SC_3_C, Jurs_WNSA_1, Jurs_WPSA_1 and decreasing CDOCKER interaction energy (E-CD), IAC_Total and Shadow_XZfrac. The predicted results shows that this model has a comparatively good predictive power which can be used in prediction of activity of new steroidal aromatase inhibitors. (C) 2010 Elsevier Masson SAS. All rights reserved.

引用

页码：5612 / 5620

页数：9

共 38 条

[1]

*ACC SOFTW INC, MAT STUD MOD

[2]

Accelrys Software Inc, DISC STUD

[3]

[Anonymous], CHEMBIOOFFICE ULTR V

[4]

Banting L, 1996, Prog Med Chem, V33, P147, DOI 10.1016/S0079-6468(08)70305-9

[5]

BANTING L, 1989, J PROG MED CHEM, V26, P253

[6]

Brueggemeier Robert W, 2002, Expert Rev Anticancer Ther, V2, P181, DOI 10.1586/14737140.2.2.181

[7] Molecular pharmacology of aromatase and its regulation by endogenous and exogenous agents [J].

Brueggemeier, RW ;

Richards, JA ;

Joomprabutra, S ;

Bhat, AS ;

Whetstone, JL .

JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY, 2001, 79 (1-5) :75-84

[8] Proteometric study of ghrelin receptor function variations upon mutations using amino acid sequence autocorrelation vectors and genetic algorithm-based least square support vector machines [J].

Caballero, Julio ;

Fernandez, Leyden ;

Garriga, Miguel ;

Abreu, Jose Ignacio ;

Collina, Simona ;

Fernandez, Michael .

JOURNAL OF MOLECULAR GRAPHICS & MODELLING, 2007, 26 (01) :166-178

[9] CYP19 (aromatase): Exploring the scaffold flexibility for novel selective inhibitors [J].

Castellano, Sabrina ;

Stefancich, Giorgio ;

Ragno, Rino ;

Schewe, Katarzyna ;

Santoriello, Marisabella ;

Caroli, Antonia ;

Hartmann, Rolf W. ;

Sbardella, Gianluca .

BIOORGANIC & MEDICINAL CHEMISTRY, 2008, 16 (18) :8349-8358

[10] Synthesis and biochemical studies of 17-substituted androst-3-enes and 3,4-epoxyandrostanes as aromatase inhibitors [J].

Cepa, Margarida M. D. S. ;

Tavares da Silva, Elisiario J. ;

Correia-da-Silva, Georgina ;

Roleira, Fernanda M. F. ;

Teixeira, Natercia A. A. .

STEROIDS, 2008, 73 (14) :1409-1415

← 1 2 3 4 →