Journal of Molecular Graphics and Modelling 2015-06-01

Aldose reductase inhibitors for diabetic complications: Receptor induced atom-based 3D-QSAR analysis, synthesis and biological evaluation.

Bhawna Vyas, Manjinder Singh, Maninder Kaur, Malkeet Singh Bahia, Amteshwar Singh Jaggi, Om Silakari, Baldev Singh

Index: J. Mol. Graph. Model. 59 , 59-71, (2015)

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Abstract

Herein, atom-based 3D-QSAR analysis was performed using receptor-guided alignment of 46 flavonoid inhibitors of aldose reductase (ALR2) enzyme. 3D-QSAR models were generated in PHASE programme, and the best model corresponding to PLS factor four (QSAR4), was selected based on different statistical parameters (i.e., Rtrain(2), 0.96; Qtest(2) 0.81; SD, 0.26). The contour plots of different structural properties generated from the selected model were utilized for the designing of five new congener molecules. These designed molecules were duly synthesized, and evaluated for their in vitro ALR2 inhibitory activity that resulted in the micromolar (IC50<22μM) activity of all molecules. Thus, the newly designed molecules having ALR inhibitory potential could be employed for the management of diabetic complications. Copyright © 2015 Elsevier Inc. All rights reserved.