化学
硫
部分
立体化学
阿卡波糖
缩醛
结构-活动关系
对接(动物)
体内
酶
分子模型
侧链
酶抑制剂
活动站点
铅化合物
体外
组合化学
生物化学
有机化学
盐(化学)
医学
护理部
生物技术
生物
聚合物
作者
Lu Lu,Jingyi Chen,Wenxiang Tao,Zhimei Wang,Dan Liú,Jiahui Zhou,Xiaoxing Wu,Haopeng Sun,Wei Li,Genzoh Tanabe,Osamu Muraoka,Bo Zhao,Liang Wu,Weijia Xie
标识
DOI:10.1021/acs.jmedchem.2c01984
摘要
We report the first attempt of double-spot structural modification on a side-chain moiety of sulfonium-type α-glucosidase inhibitors isolated from genus Salacia. A series of sulfonium salts with benzylidene acetal linkage at the C3′ and C5′ positions were designed and synthesized. In vitro enzyme inhibition evaluation showed that compounds with a strong electron-withdrawing group attached at the ortho position on the phenyl ring present stronger inhibitory activities. Notably, the most potent inhibitor 21b (1.0 mpk) can exhibit excellent hypoglycemic effects in mice, which can still compete with those of acarbose (20.0 mpk). Molecular docking of 21b demonstrated that besides conventional interacting patterns, the newly introduced benzylidene acetal moiety plays an important role in anchoring the whole molecule in a concave pocket of the enzyme. The successful identification of 21b as a lead compound for new drug discovery may provide a means for structure modification and diversification of the distinguished sulfonium-type α-glucosidase inhibitors.
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