China International Science & Technology Cooperation Base of Food Nutrition/Safety & Medicinal Chemistry, Key Laboratory of Industrial Fermentation Microbiology of Ministry of Education, College of Bioengineering, Tianjin University of Science & Technology, Tianjin 300457, PR China.
Centre de recherche de Gif-sur-Yvette, Institut de Chimie des Substances Naturelles, UPR 2301, CNRS, Avenue de la Terrasse, 91198 Gif-sur-Yvette, France.
Future Med Chem. 2018 May 1;10(9):1055-1066. doi: 10.4155/fmc-2017-0293. Epub 2018 Apr 20.
The research of novel and potent antidiabetic agents is urgently needed for the control of the exploding diabetic population. We previously reported the synthesis and antidiabetic activity of natural 8-(6"-umbelliferyl)-apigenin (1), but its antidiabetic targets are not known. Therefore, four series of derivatives were synthesized and evaluated for their antidiabetic activities. Results & methodology: Compounds (5a) and (14a) were identified as new α-glucosidase and α-amylase dual inhibitors. The kinetic analysis of the most potent α-glucosidase inhibitor of each series of compounds revealed that they inhibited α-glucosidase in irreversible modes. In addition, compounds (5a) and (14a) showed potent glucose consumption-promoting activity.
Compounds (5a) and (14a) could be regarded as promising starting points for the development of antidiabetic candidates.
为了控制糖尿病患者人数的爆炸式增长，急需研究新型强效的抗糖尿病药物。我们之前报道了天然 8-(6"-伞形基）-芹菜素（1）的合成及其抗糖尿病活性，但它的抗糖尿病靶点尚不清楚。因此，我们合成了四个系列的衍生物，并对它们的抗糖尿病活性进行了评价。结果与方法：化合物（5a）和（14a）被鉴定为新型的α-葡萄糖苷酶和α-淀粉酶双重抑制剂。对各系列化合物中最有效的α-葡萄糖苷酶抑制剂的动力学分析表明，它们以不可逆的方式抑制α-葡萄糖苷酶。此外，化合物（5a）和（14a）表现出显著的促进葡萄糖消耗活性。结论：化合物（5a）和（14a）可作为开发抗糖尿病候选药物的有前途的起点。
