Mobinikhaledi Akbar, Asghari Behvar, Jabbarpour Mahsa
Department of Chemistry, Faculty of Science, Arak University, Arak, Iran.
Department of Plant Production and Breeding Faculty of Engineering and Technology, Imam Khomeini International University, Qazvin, Iran.
Iran J Pharm Res. 2015 Summer;14(3):723-31.
In an endeavor to find a novel series of antihyperglycemic agents, new benzimidazole and pyrimidine derivatives were successfully synthesized efficiently in high yield with high purity, starting from amino acids in the presence of phosphorus oxychloride (POCl3). The synthesized compounds were identified by (1)H-NMR, (13)C-NMR, FT-IR spectroscopic techniques and elemental analysis. All products were assayed for their inhibitory effects on yeast and rat intestinal α-glucosidases. The results revealed that compounds with aromatic amino acids moiety showed significant inhibition activity on the tested enzymes. Among the benzimidazole derivatives 4c and 4d exhibited the best activity against both of the tested enzymes. Also, among the pyrimidine derivatives 5c and 5d possessed significant inhibition action on the enzymes. The IC50 values for the most potent benzimidazole yeast and intestinal α-glucosidases inhibitor (4d) were found to be 9.1 and 36.7 µM, respectively. The IC50 values for the inhibition of yeast and intestinal α-glucosidases by the most active pyrimidine compound (5d) were calculated to be 8.3 and 21.8 µM, respectively. Overall, this study proved that benzimidazole and pyrimidine derivatives with aromatic amino acids moieties can represent novel promising α-glucosidase inhibitors.
为了寻找一系列新型抗高血糖药物，以氨基酸为起始原料，在三氯氧磷（POCl3）存在下，成功高效地合成了新的苯并咪唑和嘧啶衍生物，产率高且纯度高。通过（1）H-NMR、（13）C-NMR、FT-IR光谱技术和元素分析对合成的化合物进行了鉴定。对所有产物进行了对酵母和大鼠肠道α-葡萄糖苷酶的抑制作用测定。结果表明，带有芳香族氨基酸部分的化合物对受试酶表现出显著的抑制活性。在苯并咪唑衍生物中，4c和4d对两种受试酶均表现出最佳活性。此外，在嘧啶衍生物中，5c和5d对这些酶具有显著的抑制作用。最有效的苯并咪唑酵母和肠道α-葡萄糖苷酶抑制剂（4d）的IC50值分别为9.1和36.7μM。活性最高的嘧啶化合物（5d）对酵母和肠道α-葡萄糖苷酶抑制的IC50值经计算分别为8.3和21.8μM。总体而言，本研究证明带有芳香族氨基酸部分的苯并咪唑和嘧啶衍生物可代表新型有前景的α-葡萄糖苷酶抑制剂。
