Abstract

The synthesis and antidiabetic activity of 5-Benzylidene-2,3-diarylthiazolidine-4-one derivatives (6a–w) are presented in the current work. Screening of derivatives 6a–w for their α-glucosidase inhibitory activity, showed higher inhibitory activity of twenty of the screened compounds (IC₅₀: 105–412 µM) in comparison to acarbose (IC₅₀: 750 µM) as a standard. Compounds 6r, 6b, and 6q exerted the best activity with the IC₅₀ value of 105, 110, and 127 µM, respectively. Performing the kinetic studies, revealed the competitive mode of inhibition for 6r. It binds to the active site on the enzyme and competes with the substrate for binding to the active site. based on molecular docking studies, 6b, 6q, and 6r interact with HIS280, ASP307, and PRO312 residues, which show the important role of these residues inside the active site of the enzyme. Cytotoxicity studies also showed IC₅₀ > 750 µM for 6a–w on different cell lines namely, NIH3T3, MCF-7, and HT-29.

摘要

5-Benzylidene-2,3-diarylthiazolidine-4-one 衍生物 ( 6a-w )的合成和抗糖尿病活性在当前的工作中进行了介绍。筛选衍生物6a–w的 α-葡萄糖苷酶抑制活性，与作为标准的阿卡波糖 (IC ₅₀ : 750 µM)相比，筛选出的 20 种化合物 (IC ₅₀ : 105–412 µM)显示出更高的抑制活性。化合物6r、6b和6q发挥最佳活性，IC ₅₀值分别为 105、110 和 127 µM。进行动力学研究，揭示了6r的竞争抑制模式. 它与酶上的活性位点结合并与底物竞争结合活性位点。基于分子对接研究，6b、6q和6r与 HIS280、ASP307 和 PRO312 残基相互作用，这表明这些残基在酶的活性位点内的重要作用。细胞毒性研究还表明 ，6a–w在不同细胞系（即 NIH3T3、MCF-7 和 HT-29）上的IC ₅₀ > 750 µM 。