Pentacyclic triterpene carboxylic acids derivatives integrated piperazine-amino acid complexes for α-glucosidase inhibition in vitro
Pentacyclic triterpene carboxylic acids derivatives integrated piperazine-amino acid complexes for α-glucosidase inhibition in vitro
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DOI：
10.1016/j.bioorg.2021.105212
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发表时间：
2021-07-29
影响因子：
5.1
通讯作者：
Hong, Yanping
中科院分区：
文献类型：
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作者：
Huang, Jinxiang;Zang, Xufeng;Hong, Yanping
通过在母体化合物的C-28位偶联L-氨基酸的哌嗪配合物，合成了18个五环三萜羧酸的衍生物(马斯宁酸、珊瑚油酸和积雪草酸)。并对其α-葡萄糖苷酶抑制活性进行了体外评价。结果表明，部分化合物在乙醇-水体系中的抑制活性(15E IC50=591µM，16E IC_(50)=423µM)与阿卡波糖(IC_(50)=347µM)相近。此外，在以DMSO为溶剂的测定体系中，化合物16E(IC_(50)=380µM)比阿卡波糖(IC_(50)=493µM)表现出更好的抑制活性。两种不同溶剂体系的比较表明，它们在DMSO体系中比在乙醇-水体系中具有更好的α-葡萄糖苷酶抑制活性。遗憾的是，所有合成的衍生物在两种测试溶剂体系中都表现出低于母体化合物的α-葡萄糖苷酶抑制活性。酶动力学结果表明，化合物16E的抑制机理为非竞争性抑制，其抑制常数K-I=552uM。
Eighteen derivatives of pentacyclic triterpene carboxylic acids (Maslinic acid, Corosolic acid and Asiatic acid) have been prepared by coupling the piperazine complex of L-amino acids at the C-28 site of the parent compounds. The alpha-glucosidase inhibitory activities of the pristine derivatives were evaluated in vitro. The results indicated that the inhibitory activity of some compounds (15e IC50 = 591 mu M, 16e IC50 = 423 mu M) was closed to that of the reference acarbose (IC50 = 347 mu M) in ethanol-water system. In addition, compound 16e (IC50 = 380 mu M) showed superior inhibitory activity than acarbose (IC50 = 493 mu M) in the measurement system with DMSO as solvent. The comparison of two different solvent systems showed that the derivatives had better alpha-glucosidase inhibitory activity in the DMSO system than that of in ethanol-water system. Regrettably, all of the as synthesized derivatives exhibited inferior alpha-glucosidase inhibitory activities than those of the parent compounds in both test solvent systems. Furthermore, the result of enzyme kinetics demonstrated that the inhibition mechanism of compound 16e was noncompetitive inhibition with the inhibition constant K-i = 552 mu M.