Gaussian field-based comparative 3D QSAR modelling for the identification of favourable pharmacophoric features of chromene derivatives as selective inhibitors of ALR2 over ALR1

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dc.contributor.authorVerma, Sant Kumar
dc.contributor.authorKumar, Niraj
dc.contributor.authorThareja, Suresh
dc.date.accessioned2024-01-21T10:38:14Z
dc.date.accessioned2024-08-13T12:05:09Z
dc.date.available2024-01-21T10:38:14Z
dc.date.available2024-08-13T12:05:09Z
dc.date.issued2021-01-07T00:00:00
dc.description.abstractAldehyde reductase (ALR1) and aldose reductase (ALR2) are both oxo-reductase enzymes of aldo-keto reductase (AKR) superfamily involved in several cellular processes. ALR1 plays an important role in colorectal cancer, lungs, and hepatic carcinoma, while ALR2 is involved in diabetic complications like retinopathy, neuropathy, and nephropathy cataract. Both the enzymes take part in distinct physiological processes, however, share more > 70% structural homology. This is the major cause behind the unachieved target selectivity of molecules that entered the development pipeline as ALR2 inhibitors. Chromene analogues have been widely explored for diverse biological activities, including antioxidant and diabetic complication prevention potential. For the identification of spatial fingerprints of target-specific chromene bearing ALR2 inhibitors over ALR1, Gaussian field-based comparative 3D QSAR models were generated on a dataset having ALR1 and ALR2 inhibitory activity. Both the ALR1 and ALR2 3D QSAR models were statistically fit with good predictive ability concerning PLS generated validation constraints. The comparative steric, electrostatic, hydrophobic, HBA, and HBD features were elucidated using respective contour maps for selective target specific favourable activity against ALR2 over ALR1. In addition, the five-point pharmacophores for ALR1 and ALR2 favourable features were also generated using the DHHRR_1 hypothesis for better insight on the distinctive features of ALR2 inhibitors compared to ALR1. � 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.en_US
dc.identifier.doi10.1007/s11224-020-01714-6
dc.identifier.issn10400400
dc.identifier.urihttp://10.2.3.109/handle/32116/3505
dc.identifier.urlhttps://link.springer.com/10.1007/s11224-020-01714-6
dc.language.isoen_USen_US
dc.publisherSpringeren_US
dc.subjectAldehyde reductase (ALR1)en_US
dc.subjectAldose reductase (ALR2)en_US
dc.subjectChromeneen_US
dc.subjectDiabetic complicationsen_US
dc.subjectGaussian field-based 3D QSARen_US
dc.subjectPharmacophore mappingen_US
dc.titleGaussian field-based comparative 3D QSAR modelling for the identification of favourable pharmacophoric features of chromene derivatives as selective inhibitors of ALR2 over ALR1en_US
dc.title.journalStructural Chemistryen_US
dc.typeArticleen_US
dc.type.accesstypeClosed Accessen_US

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