RESUMEN
AIM: Targeting aldose reductase enzyme with 2,4-thiazolidinedione-3-acetic acid derivatives having a bulky hydrophobic 3-arylquinazolinone residue. MATERIALS & METHODS: All the target compounds were structurally characterized by different spectroscopic methods and microanalysis, their aldose reductase inhibitory activities were evaluated, and binding modes were studied by molecular modeling. RESULTS: All the synthesized compounds proved to inhibit the target enzyme potently, exhibiting IC50 values in the nanomolar/low nanomolar range. Compound 5i (IC50 = 2.56 nM), the most active of the whole series, turned out to be almost 70-fold more active than the only marketed aldose reductase inhibitor epalrestat. CONCLUSION: This work represents a promising matrix for developing new potential therapeutic candidates for prevention of diabetic complications through targeting aldose reductase enzyme. [Formula: see text].