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

Abstract

In the search for small-molecule aldose reductase (AR) inhibitors, new tetrazolehydrazone hybrids (1-15) were designed. An efficient procedure was employed for the synthesis of compounds 1-15. All hydrazones were subjected to an in vitro assay to assess their AR inhibitory profiles. Compounds 1-15 caused AR inhibition with K i values ranging between 0.177 and 6.322 µM and IC 50 values ranging between 0.210 and 0.676 µM. 2-[(1-(4-Hydroxyphenyl)-1H-tetrazol-5-yl)thio]-N'-(4-fluorobenzylidene) acetohydrazide ( 4) was the most potent inhibitor of AR in this series. Compound 4 markedly inhibited AR (IC 50 = 0.297 µM) in a competitive manner (K i = 0.177 µM) compared to epalrestat (K i = 0.857 µM, IC 50 = 0.267 µM). Based on the in vitro data obtained by applying the MTT test, compound 4 showed no cytotoxic activity toward normal (NIH/3T3) cells at the tested concentrations, indicating its safety as an AR inhibitor. Compound 4 exhibited proper interactions with crucial amino acid residues within the active site of AR. In silico QikProp data of all hydrazones (1-15) were also determined to assess their pharmacokinetic profiles. Taken together, compound 4 stands out as a promising inhibitor of AR for further in vivo studies.

Naringenin, Hesperidin and Quercetin Ameliorate Radiation‐Induced Damage In Rats: In Vivo And In Silico Evaluations

“…Because of its polar nature, sorbitol finds it challenging to diffuse across cell membranes, which leads to osmotic imbalance [55] . This causes tissue damage from osmotic swelling and lens fiber cell rupture, which in turn leads to the development of cataracts [56,57] . In this study, the eye AR enzyme activity level of the studied groups are presented in Figure 2.…”

“…[55] This causes tissue damage from osmotic swelling and lens fiber cell rupture, which in turn leads to the development of cataracts. [56,57] In this study, the eye AR enzyme activity level of the studied groups are presented in Figure 2.…”

Exploration of Some Bis‐Sulfide and Bis‐Sulfone Derivatives as Non‐Classical Aldose Reductase İnhibitors

“…In the final reaction mixture, DMSO was present at a concentration of around 1 % [89] . To investigate the in vitro inhibitory mechanisms of these bis‐sulfides ( 5 a – i ) and bis‐sulfones ( 6 a – i ) against ALR2 [90–92] , the kinetic tests were conducted using Cerelli's method [93] at 340 nm, spectrophotometrically, and the DL‐glyceraldehyde (PubChem CID: 79014) was used as the substrate [94–97] . All the samples were measured three times.…”

“…[89] To investigate the in vitro inhibitory mechanisms of these bis-sulfides (5 a-i) and bis-sulfones (6 a-i) against ALR2 [90][91][92] , the kinetic tests were conducted using Cerelli's method [93] at 340 nm, spectrophotometrically, and the DL-glyceraldehyde (PubChem CID: 79014) was used as the substrate. [94][95][96][97] All the samples were measured three times. In accordance with our earlier research, IC 50 plots and Lineweaver-Burk curves [98] were made, and K I constants, their coefficient of determination (R 2 ), and inhibition types were determined based on the observed data.…”

Screening of in Vitro Inhibition of Lactoperoxidase Enzyme by Methyl Benzoate Derivatives with Molecular Docking Studies

“…The Small-Molecule Drug Discovery Suite 2022-3 for Mac (Schrödinger, LLC, NY, USA) was utilized to conduct in silico molecular docking study, as previously reported. [41,42] This suite includes the Maestro, Protein Preparation Wizard, [43,44] SiteMap, [45] LigPrep, [46] Receptor Grid Generation, [47] Ligand Docking, [48] and Prime MM-GBSA [49,50] tools. The Protein Data Bank (http://www.…”