Medicinal Plants Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; Persian Medicine and Pharmacy Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran.
Bioorg Chem. 2019 Mar;83:161-169. doi: 10.1016/j.bioorg.2018.10.023. Epub 2018 Oct 11.
A novel series of quinazolinone-1,2,3-triazole hybrids 10a-p were designed, synthesized, and evaluated for their in vitro α-glucosidase inhibitory activity leading to efficient anti-diabetic agents. All synthesized compounds exhibited good inhibitory activity against yeast α-glucosidase (IC values in the range of 181.0-474.5 µM) even much more potent than standard drug acarbose (IC = 750.0). Among them, quinazolinone-1,2,3-triazoles possessing 4-bromobenzyl moiety connected to 1,2,3-triazole ring (10g and 10p) demonstrated the most potent inhibitory activity towards α-glucosidase. Compound 10g inhibited α-glucosidase in a competitive manner with K value of 117 µM. Furthermore, the binding modes of the most potent compounds 10g and 10p in the α-glucosidase active site was studied through in silico docking studies. Also, lack of cytotoxicity of compounds 10g and 10p was confirmed via MTT assay.
我们设计、合成了一系列新型的喹唑啉酮-1,2,3-三唑杂合体 10a-p，并对其体外α-葡萄糖苷酶抑制活性进行了评估，以期得到高效的抗糖尿病药物。所有合成的化合物对酵母α-葡萄糖苷酶均表现出良好的抑制活性（IC 值在 181.0-474.5 µM 范围内），甚至比标准药物阿卡波糖（IC = 750.0）更有效。其中，具有连接到 1,2,3-三唑环的 4-溴苄基部分的喹唑啉酮-1,2,3-三唑类化合物（10g 和 10p）对α-葡萄糖苷酶表现出最强的抑制活性。化合物 10g 以竞争性方式抑制α-葡萄糖苷酶，K 值为 117 µM。此外，通过计算机对接研究进一步研究了最有效化合物 10g 和 10p 在α-葡萄糖苷酶活性部位的结合模式。而且，通过 MTT 测定法证实了化合物 10g 和 10p 缺乏细胞毒性。
