A new series of hydrazones as small‐molecule aldose reductase inhibitors

• DOI: 10.1002/ardp.202200570
• Publication Date: 2023-01-05T20:40:31Z
• Authors: Mehlika D. Altıntop; Yeliz Demir; Cüneyt Türkeş; Remzi B. Öztürk; Zerrin Cantürk; Şükrü Beydemir; Ahmet Özdemir
• Keywords: Hydrazone; IC50; Thio-; Tetrazole

In the search for small-molecule aldose reductase (AR) inhibitors, new tetrazole-hydrazone hybrids (1-15) were designed. An efficient procedure was employed synthesis of compounds 1-15. All hydrazones subjected to an in vitro assay assess their AR inhibitory profiles. Compounds 1-15 caused inhibition with Ki values ranging between 0.177 and 6.322 µM IC50 0.210 0.676 µM. 2-[(1-(4-Hydroxyphenyl)-1H-tetrazol-5-yl)thio]-N'-(4-fluorobenzylidene)acetohydrazide (4) most potent inhibitor this series. Compound 4 markedly inhibited (IC50 = 0.297 µM) a competitive manner (Ki compared epalrestat 0.857 µM, 0.267 µM). Based on data obtained by applying MTT test, compound showed no cytotoxic activity toward normal (NIH/3T3) cells at tested concentrations, indicating its safety as inhibitor. exhibited proper interactions crucial amino acid residues within active site AR. silico QikProp all also determined pharmacokinetic Taken together, stands out promising further vivo studies.