Faculty of Pharmacy, Kindai University, 3-4-1 Kowakae, Higashi-osaka, Osaka 577-8502, Japan.
Pharmaceutical Research and Technology Institute, Kindai University, 3-4-1 Kowakae, Higashi-osaka, Osaka 577-8502, Japan.
Bioorg Med Chem Lett. 2021 Feb 1;33:127751. doi: 10.1016/j.bmcl.2020.127751. Epub 2020 Dec 19.
Four chain-extended analogs (12a-12d) and two related de-O-sulfonated analogs (13a and 13c) by introducing alkyl groups (a: R = CH, b R = CH, c: R = CH, d: R = CH) to the side chains of salacinol (1), a natural α-glucosidase inhibitor from Ayurvedic traditional medicine "Salacia", were synthesized. The α-glucosidase inhibitory activities of all the synthesized analogs were evaluated in vitro. Against human intestinal maltase, the inhibitory activities of 12a and 13a with seven-carbon side chain were equal to that of 1. In contrast, analogs (12b-12d, and 13c) exhibited higher level of inhibitory activity against the same enzyme than 1 and had equal or higher potency than those of the clinically used anti-diabetics, voglibose, acarbose, and miglitol. Thus, elongation of the side chains of 1 was effective for specifically increasing the inhibitory activity against human intestinal maltase.
四个链延伸类似物（12a-12d）和两个相关的去-O-磺化类似物（13a 和 13c）通过向天然 α-葡萄糖苷酶抑制剂 salacinol（1）的侧链中引入烷基（a：R=CH，b R=CH，c：R=CH，d：R=CH）来自印度传统医学“Salacia”。合成了所有合成类似物的体外α-葡萄糖苷酶抑制活性进行了评价。对人肠麦芽糖酶，具有七个碳侧链的 12a 和 13a 的抑制活性与 1 相等。相比之下，类似物（12b-12d 和 13c）对同一酶的抑制活性高于 1，并且与临床使用的抗糖尿病药物 voglibose、阿卡波糖和米格列醇的效力相等或更高。因此，1 的侧链延长对于特异性增加对人肠麦芽糖酶的抑制活性是有效的。
