Series of novel analogs, which were primarily modified on its lactone moiety, was synthesized based on Andrographolide (1), a natural product sesquiterpene inhibitor of α-glucosidase. Among new analogs, 14-deoxy-11,12-didehydro-15-(4-ethoxybenzylidene)andrographolide (3h) was determined to have the greatest potential of α-glucosidase inhibitor through the calculation of IC₅₀ value of 160 ± 5.1 μM, a significant improvement compared to the clinical dose of Acarbose, which showed the IC₅₀ value of 390 ± 8.1 μM. In addition, 14-deoxy-11,12-didehydro-3,19-(2′-hydroxybenzylidene)-15-(2-hydroxybenzylidene) andrographolide (7), a 15-benzylidene derivative of 14-deoxy-11,12-didehydroandrographolide containing a 1,3-dioxane moiety at C(3) and C(19), also displayed good inhibition with IC₅₀ 260 ± 13 μM. These results are promising avenues in the subsequent optimization of antidiabetic drugs.

中文翻译：

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穿心莲内酯衍生物的制备及其对α-葡萄糖苷酶的抑制作用

基于穿心莲内酯（1），一种天然产物倍半萜烯α-葡萄糖苷酶抑制剂，合成了一系列主要在其内酯部分上进行了修饰的新型类似物。在新的类似物中，通过计算160±5.1μM的IC ₅₀值，可以确定14-脱氧11,12-二氢15-（4-乙氧基苄叉基）和穿心莲内酯（3h）具有最大的α-葡萄糖苷酶抑制剂潜力，与阿卡波糖的临床剂量相比有显着改善，后者的IC ₅₀值为390±8.1μM。此外，14-脱氧-11,12-二氢-3,19-（2'-羟基亚苄基）-15-（2-羟基亚苄基）穿心莲内酯（7），在C（3）和C（19）处含有1,3-二恶烷部分的14-脱氧-11,12-二氢-穿心莲内酯的15-亚苄基衍生物也显示出良好的抑制作用，IC ₅₀ 260±13μM。这些结果是随后优化抗糖尿病药物的有希望的途径。