Novel piperazine–pyridine conjugates as aldose reductase inhibitors: synthesis, DFT analysis, molecular docking, ADME evaluation, DPPH radical scavenging activity, and in vitro aldose reductase inhibitory activity

INTRODUCTION: Piperazine-pyridine-conjugated analogs were synthesized and evaluated for aldose reductase inhibition for treating diabetes mellitus. MATERIALS AND METHODS: All synthesized compounds were structurally characterized by spectral studies. In addition, in silico ADME and cardiotoxicity predictions, molecular docking studies against aldose reductase (4JIR), and density functional theory (DFT) analysis were performed to evaluate the pharmacokinetic properties, binding interactions, and electronic characteristics of the synthesized compounds. The compounds were subsequently evaluated for DPPH Scavenging and aldose reductase inhibitory activity. RESULTS: = 10.5 ± 0.44 µM) under the experimental conditions. Additionally, the synthesized compounds showed measurable DPPH radical scavenging activity, as a supportive assessment of antioxidant potential relevant to oxidative stress associated with diabetic complications.