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

• We developed atom-based 3D-QSAR model for flavonoid aldose reductase inhibitors.
• Developed model was validated using various statistical parameters.
• New molecules were designed on the basis of contour plots obtained from generated model.
• The designed molecules were synthesized and evaluated for ALR2 inhibitory activity.

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  ., Rtrain2, 0.96; Qtest2 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 < 22 μM) activity of all molecules. Thus, the newly designed molecules having ALR inhibitory potential could be employed for the management of diabetic complications.

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