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In this article, different s-substituted benzimidazole-thioquinoline derivatives were designed, synthesized, and evaluated for their possible α-glucosidase inhibitory activities. The most active compound in this series, 6j (X = 4-bromobenzyl) exhibited significant potency with an IC 50 value of 28.0 ± 0.6 µM compared to acarbose as the positive control with an IC 50 value of 750.0 µM. The kinetic study showed a competitive inhibition pattern against α-glucosidase for the 6j derivative. Also, the molecular dynamic simulations were performed to determine key interactions between compounds and the targeted enzyme. The in silico pharmacodynamics and ADMET properties were executed to illustrate the druggability of the novel derivatives. In general, it can be concluded that these derivatives can serve as promising leads to the design of potential α-glucosidase inhibitors., (© 2023. The Author(s).)

In this study, new hybrids of quinazolinone-1,2,3-triazole-acetamide were designed, synthesized, and screened for their α-glucosidase inhibitory activity. The results obtained from the in vitro screening indicated that all analogs exhibited significant inhibitory activity against α-glucosidase (IC 50 values ranging from 4.8-140.2 μM) in comparison to acarbose (IC 50 = 750.0 μM). The limited structure-activity relationships suggested the variation in the inhibitory activities of the compounds affected by different substitutions on the aryl moiety. The enzyme kinetic studies of the most potent compound 9c, revealed that it inhibited α-glucosidase in a competitive mode with a K i value of 4.8 μM. In addition, molecular docking studies investigated the structural perturbation and behavior of all derivatives inside the α-glucosidase active site. Next, molecular dynamic simulations of the most potent compound 9c, were performed to study the behavior of the 9c-complex during the time. The results showed that these compounds can be considered as potential antidiabetic agents., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

A series of aryl phenoxy methyl triazole conjugated with thiosemicarbazides were designed, synthesized, and evaluated for their tyrosinase inhibitory activities in the presence of l-dopa and l-tyrosine as substrates. All the compounds showed tyrosinase inhibition in the sub-micromolar concentration. Among the derivatives, compound 9j bearing benzyl displayed exceptionally high potency against tyrosinase with IC 50 value of 0.11 μM and 0.17 μM in the presence of l-tyrosine and l-dopa as substrates which is significantly lower than that of kojic acid as the positive control with an IC 50 value of 9.28 μM for l-tyrosine and 9.30 μM for l-dopa. According to Lineweaver-Burk plot, 9j demonstrated an uncompetitive type of inhibition in the kinetic assay. Also, in vitro antioxidant activities determined by DPPH assay recorded an IC 50 value of 68.43 μM for 9i. The melanin content of 9j was determined on B16F10 melanoma human cells which demonstrated a significant reduction of the melanin content. Moreover, the binding energies corresponding to the same ligand as well as computer-aided drug-likeness and pharmacokinetic studies were also carried out. Compound 9j also possessed metal chelation potential correlated to its high anti-TYR activity., (Copyright © 2021 Elsevier Inc. All rights reserved.)