title: A novel combined pharmacophore mapping and quantitative structure selectivity relationship analysis for the development of potent and selective human aldose reductase inhibitors.
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.
authors.affiliation: Department of Chemistry, Punjabi University, Patiala, Punjab 147002, India. bhawnaom@rediffmail.com
authors.forename: Bhawna
authors.initials: B
authors.lastname: Vyas
authors.forename: Baldev
authors.initials: B
authors.lastname: Singh
authors.forename: Om
authors.initials: O
authors.lastname: Silakari
mesh_terms: D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D017076:Computer-Aided Design; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D008958:Models, Molecular; D021281:Quantitative Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D000449:Aldehyde Reductase