Rhodanine-3-acetamide derivatives as aldose and aldehyde reductase inhibitors to treat diabetic complications: synthesis, biological evaluation, molecular docking and simulation studies

Abstract In diabetes, increased accumulation of sorbitol has been associated with diabetic complications through polyol pathway. Aldose reductase (AR) is one the key factors involved in reduction glucose to sorbitol, thereby its inhibition important for management complications. present study, a series seven 4-oxo-2-thioxo-1,3-thiazolidin-3-yl acetamide derivatives 3 ( a–g ) were synthesized by reaction 5-(4-hydroxy-3-methoxybenzylidene)-4-oxo-2-thioxo-1,3-thiazolidin-3-yl acetic acid 2a and 5-(4-methoxybenzylidene)-4-oxo-2-thioxo-1,3-thiazolidin-3-yl 2b different amines. The compounds investigated their vitro aldehyde (ALR1) aldose (ALR2) enzyme inhibitory potential. Compound 3c , 3d 3e 3f showed ALR1 at lower micromolar concentration whereas all more active than standard inhibitor valproic acid. Most against ALR2 but compound 3a higher drug sulindac. Overall, most potent was an 0.12 ± 0.01 µM. results that vanillin exhibited better activity both reductase. molecular docking studies carried out investigate binding affinities ALR2. site analysis revealed similar interactions as found cognate ligands within sites enzymes.