Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Shanghai 201203, China.
School of Pharmacy, University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, China.
Molecules. 2020 Aug 14;25(16):3709. doi: 10.3390/molecules25163709.
We selectively oxidized the C-23 hydroxyl group in an asiatic acid (AA) derivative and then, for the first time with AA, modification of the C-23 carboxyl group was conducted to synthesize a series of new AA derivatives. The evaluation of their cytotoxic activities against two human cancer cell lines (SKOV-3 and HCT116) using the MTT assay in vitro revealed a distinctive structure activity relationship (SAR) associated with the intramolecular hydrogen bonding of the amide moiety at C-23. According to the established SAR, the cytotoxic activities of four promising compounds were then evaluated against MCF-7, A549, A2780, HepG2 and HL-60 cancer cell lines. Compound had the best cytotoxic activity among all tested derivatives in the HL-60 cell line, giving IC = 0.47 μM, while showing no cytotoxic effect against human normal cells (HUVEC).
我们选择性地氧化了一个亚洲酸 (AA) 衍生物中的 C-23 羟基，然后，首次使用 AA，对 C-23 羧基进行了修饰，合成了一系列新的 AA 衍生物。通过体外 MTT 法评估它们对两种人癌细胞系 (SKOV-3 和 HCT116) 的细胞毒性活性，发现与 C-23 酰胺部分的分子内氢键相关的独特结构活性关系 (SAR)。根据建立的 SAR，然后评估了四种有前途的化合物对 MCF-7、A549、A2780、HepG2 和 HL-60 癌细胞系的细胞毒性活性。在 HL-60 细胞系中，所有测试的衍生物中化合物表现出最好的细胞毒性活性，IC = 0.47 μM，而对人正常细胞 (HUVEC) 没有细胞毒性作用。
