Exploiting oxadiazole-sulfonamide hybrids as new structural leads to combat diabetic complications via aldose reductase inhibition

N‐substituted phthalazine sulfonamide derivatives as non‐classical aldose reductase inhibitors

“…In this direction, many recent studies have indicated that sulfonamide derivatives exhibit effective inhibition against AR. In this context, the study by Javid et al 33 reported a series of oxadiazole‐sulfonamide hybrids 6(a‐l) synthesized through multistep reaction and later screened against AR. Most of the compounds exhibited good results; among them, 6b , 6e , 6f , and 6l were the most prominent.…”

“…In this direction, many recent studies have indicated that sulfonamide derivatives exhibit effective inhibition against AR. In this context, the study by Javid et al 33 Interestingly, compound 5e interacted, through water-mediated contact, with Leu300 (distance 2.41 Å) while establishing an additional Hbond through the sulfonyl oxygen with Ser302 (distance 2.22 Å), as well as π-π stacking interaction formed with Phe122 and Trp219. Specifically, compound 5f is easily accommodated in the hydrophobic cavity of the binding site targeting, besides the identical hydrophobic residues listed above, also Leu121 and Leu124 (Figures 4 and 5).…”

β-Aldehyde ketones as dual inhibitors of aldose reductase and α-glucosidase with antioxidant properties

“…For further study of the antioxidant activity of the compounds, lipid peroxidation was examined by the quantitative analysis of malondialdehyde (MDA) with thiobarbituric acid (TBARS) where the product of lipid peroxidation was present in mouse brain tissues. 51,52 The results listed in Table 4 show the apparent suppression of lipid peroxidation with the baldehyde ketone group (9). Compound 5l yet again appeared to be the most active compound in the inhibition of TBARS production because the inhibition rate of MDA was 74.8% at a concentration of 10 mM of 5l, whereas that of trolox was only 27.40%.…”

“…8 Normally glucose is mainly transformed into glucose–6-phosphate with hexokinase and then enters the glycolytic pathway. 9 However, under hyperglycemia conditions, the hexokinase is rapidly saturated and a significant portion of non-phosphorylated glucose is metabolized through the polyol pathway, as shown in Fig. 1.…”

Research progress on the synthesis and pharmacology of 1,3,4-oxadiazole and 1,2,4-oxadiazole derivatives: a mini review

“…Compound 30a inhibited ALR1 selectively with an IC 50 value of 4.77 ± 0.47 µM, whereas compound 30c inhibited ALR2 selectively with an IC 50 value of 2.21 ± 0.73 µM. The remaining analogs inhibited both enzymes in tandem 37 .…”