Current Computer-Aided Drug Design

Subhash C. Basak
Departments of Chemistry, Biochemistry & Molecular Biology University of Minnesota Duluth
Duluth, MN 55811


A Novel Combined Pharmacophore Mapping and Quantitative Structure Selectivity Relationship Analysis for the Development of Potent and Selective Human Aldose Reductase Inhibitors

Author(s): Bhawna Vyas, Baldev Singh, Om Silakari.


Present study describes the use of multiple pharmacophore mapping and three dimensional quantitative structure selectivity relationship (3D-QSSR) analysis for human aldose reductase (hALR2) and human aldehyde reductase (hALR1) inhibitors to develop selective molecules against hALR2. Two pharmacophore models one each for highly active hALR2 inhibitors and highly active hALR1 inhibitors were generated. Atom based 3D-QSSR analysis was performed employing docking based alignment of molecules. Sequential multi-step virtual screening was performed to screen PHASE database of approximately 1.5 million molecules. Finally, 22 potent and highly selective hALR2 inhibitors were obtained as potential hits using virtual screening protocol. This study of multiple pharmacophore mapping combined with 3D-QSSR analysis provided deep insight into the structural features requirement for selectivity and may be used as novel tool to design new selective and potent hALR2 inhibitors.

Keywords: PHASE, hALR2, hALR1, diabetic complications, polyol pathway.

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Article Details

Year: 2013
Page: [371 - 384]
Pages: 14
DOI: 10.2174/1573409911309030008
Price: $58