摘要
目的:从谷物植物化学物中筛选潜在的人源α-葡萄糖苷酶抑制剂。方法:构建小分子数据库,采用分子对接结合ADME和Lipinski性质从265种中筛选出了10种具有人源α-葡萄糖苷酶抑制潜力的植物化学物。结果:体外抑制活性实验结果显示牡荆素和异牡荆素两种常见碳苷黄酮及其苷元芹菜素抑制酵母源α-葡萄糖苷酶活力的能力为芹菜素>牡荆素>异牡荆素,与分子对接打分结果不一致。进一步的分子动力学和弱相互作用分析结果表明,虽然上述3种植物化学物都能与关键氨基酸残基稳定结合,但可能是结构中的糖苷取代增大了立体位阻效应,使后两者在活性口袋中的运动轨迹范围不同于芹菜素,导致三者产生活性差异。结论:研究可为从谷物植物化学物中筛选人源α-葡萄糖苷酶抑制剂及结构改造提供依据。
The present study aimed to screen potential humanα-glucosidase inhibitors from cereal phytochemicals.A database containing 265 cereal phytochemicals was established and 10 cereal phytochemicals withα-glucosidase inhibitory potential were selected according to the molecular docking results combined with their ADME and Lipinski properties.Results showed that the inhibitory activity of apigenin and two common C-glycosylated flavones,vitexin and isovitexin,onα-glucosidase from Saccharomyces cerevisiae decreased in that order,which is inconsistent with the molecular docking results.Further molecular dynamic and weak interaction analysis revealed that while all the above phytochemicals could stably bind to the key amino acid residues,their anti-α-glucosidase activities differed from one another,which may be due to the fact that glycoside substitution enhanced the steric hindrance and as a result,the movement trajectory of vitexin and isovitexin in the active pocket ofα-glucosidase differed from that of apigenin.These results will provide a scientific basis for the screening and structural modification of humanα-glucosidase inhibitors from cereal phytochemicals.
作者
石嘉怿
张冉
梁富强
程玉鑫
张太
SHI Jiayi;ZHANG Ran;LIANG Fuqiang;CHENG Yuxin;ZHANG Tai(College of Food Science and Engineering,Nanjing University of Finance and Economics,Nanjing 210023,China;College of Food Science and Technology,Huazhong Agricultural University,Wuhan 430070,China)
出处
《食品科学》
EI
CAS
CSCD
北大核心
2021年第5期9-16,共8页
Food Science
基金
国家自然科学基金青年科学基金项目(32001702)。
