Abstract
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.
Current Computer-Aided Drug Design
Title:A Novel Combined Pharmacophore Mapping and Quantitative Structure Selectivity Relationship Analysis for the Development of Potent and Selective Human Aldose Reductase Inhibitors
Volume: 9 Issue: 3
Author(s): Bhawna Vyas, Baldev Singh and Om Silakari
Affiliation:
Keywords: PHASE, hALR2, hALR1, diabetic complications, polyol pathway.
Abstract: 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.
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Vyas Bhawna, Singh Baldev and Silakari Om, A Novel Combined Pharmacophore Mapping and Quantitative Structure Selectivity Relationship Analysis for the Development of Potent and Selective Human Aldose Reductase Inhibitors, Current Computer-Aided Drug Design 2013; 9 (3) . https://dx.doi.org/10.2174/1573409911309030008
DOI https://dx.doi.org/10.2174/1573409911309030008 |
Print ISSN 1573-4099 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6697 |
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