Pursuing Aldose Reductase Inhibitors through in Situ Cross-Docking and Similarity-Based Virtual Screening

被引：37

作者：

Cosconati, Sandro ^{[1
]}

Marinelli, Luciana ^{[1
]}

La Motta, Concettina ^{[2
]}

Sartini, Stefania ^{[2
]}

Da Settimo, Federico ^{[2
]}

Olson, Arthur J. ^{[3
]}

Novellino, Ettore ^{[1
]}

机构：

[1] Univ Naples Federico II, Dipartimento Chim Farmaceut & Tossicol, I-80131 Naples, Italy

[2] Univ Pisa, Dipartimento Sci Farmaceut, I-56126 Pisa, Italy

[3] Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2009年 / 52卷 / 18期

关键词：

MOLECULAR DOCKING; MULTIPLE TARGETS; COMPLICATIONS;

D O I：

10.1021/jm901045w

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Aldose reductase (ALR2) is a critical enzyme in the development of the major complications of diabetes mellitus. Herein, new molecular entities active against ALR2 were discovered through an integrated receptor- and ligand-based virtual screening campaign. Twelve candidates were found to inhibit this enzyme in the micromolar range including two ligands having an IC50 below 3 mu M. Six new compounds, structurally unrelated to the known ARIs, have been identified, opening up opportunity for lead optimization.

引用

页码：5578 / 5581

页数：4

共 20 条

[1] Molecular similarity searching using atom environments, information-based feature selection, and a naive Bayesian classifier [J].

Bender, A ;

Mussa, HY ;

Glen, RC ;

Reiling, S .

JOURNAL OF CHEMICAL INFORMATION AND COMPUTER SCIENCES, 2004, 44 (01) :170-178

[2] Genetic analysis of aldose reductase in diabetic complications [J].

Chung, SSM ;

Chung, SK .

CURRENT MEDICINAL CHEMISTRY, 2003, 10 (15) :1375-1387

[3]

Costantino L, 1999, MED RES REV, V19, P3, DOI 10.1002/(SICI)1098-1128(199901)19:1<3::AID-MED2>3.0.CO

[4]

2-7

[5]

Ho ECM, 2001, DIABETES, V50, pA59

[6] Ultrahigh resolution drug design I:: Details of interactions in human aldose reductase-inhibitor complex at 0.66 Å [J].

Howard, EI ;

Sanishvili, R ;

Cachau, RE ;

Mitschler, A ;

Chevrier, B ;

Barth, P ;

Lamour, V ;

Van Zandt, M ;

Sibley, E ;

Bon, C ;

Moras, D ;

Schneider, TR ;

Joachimiak, A ;

Podjarny, A .

PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS, 2004, 55 (04) :792-804

[7] Benchmarking sets for molecular docking [J].

Huang, Niu ;

Shoichet, Brian K. ;

Irwin, John J. .

JOURNAL OF MEDICINAL CHEMISTRY, 2006, 49 (23) :6789-6801

[8] A semiempirical free energy force field with charge-based desolvation [J].

Huey, Ruth ;

Morris, Garrett M. ;

Olson, Arthur J. ;

Goodsell, David S. .

JOURNAL OF COMPUTATIONAL CHEMISTRY, 2007, 28 (06) :1145-1152

[9] Global burden of diabetes, 1995-2025 - Prevalence, numerical estimates, and projections [J].

King, H ;

Aubert, RE ;

Herman, WH .

DIABETES CARE, 1998, 21 (09) :1414-1431

[10] Virtual screening for inhibitors of human aldose reductase [J].

Kraemer, O ;

Hazemann, I ;

Podjarny, AD ;

Klebe, G .

PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS, 2004, 55 (04) :814-823

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