In this study, indolyl-1,2,4-oxidizable derivatives were synthesized and in vitro evaluated as new class of non-competitive α-glucosidase inhibitors. Most of the compounds showed better inhibitory activity than reference drug (acarbose), with compound 35 being the most potent inhibitor. Kinetic analysis indicated that compound 35 had non-competitive inhibition on α-glucosidase, and fluorescence quenching experiment confirmed the direct binding of 35 to α-glucosidase. Besides, some selected compounds had no effect on cell viability of human normal hepatocyte (LO2) and human liver cancer (HepG2) cells. Thus, this work provides a new chemotype for developing novel drugs against type 2 diabetes.

在这项研究中，吲哚基-1,2,4-可氧化衍生物被合成并在体外评估为一类新的非竞争性α-葡萄糖苷酶抑制剂。大多数化合物显示出比参考药物（阿卡波糖）更好的抑制活性，其中化合物 35 是最有效的抑制剂。动力学分析表明化合物35对α-葡萄糖苷酶具有非竞争性抑制作用，荧光猝灭实验证实35与α-葡萄糖苷酶直接结合。此外，一些选定的化合物对人正常肝细胞 (LO2) 和人肝癌 (HepG2) 细胞的细胞活力没有影响。因此，这项工作为开发针对 2 型糖尿病的新型药物提供了一种新的化学型。