School of Pharmaceutical Sciences, Jilin University, Changchun 130021, China.
Molecules. 2012 Jan 31;17(2):1278-91. doi: 10.3390/molecules17021278.
Rotundic acid (RA, 1), a natural compound, exhibits potent tumor cell growth inhibiting properties. To date there are no reports on derivatives of RA. Furthermore, the 28-COOH position of RA might make it unstable and induced serious gastrointestinal side effects when it was applied in vivo. Therefore, in order to explore and make use of this compound, eight new amino acid derivatives of RA at the 28-COOH position were synthesized and evaluated for their cytotoxicities in vitro on three tumor cell lines including A375, HepG2 and NCI-H446. As a result, a few of these new amino acid derivatives showed stronger cytotoxicity. Compound 5a was found to have the best inhibition activity on the three tested human tumor cell lines with IC(50) values of less than 10 μM compared with RA treatment. Meanwhile, the cytotoxicity of compound 6b was significantly higher than that of RA on the A375 cell line and almost the same as RA on the HepG2 and NCI-H446 cell lines. Hence, compounds 5a and 6b may serve as potential lead compounds for the development of new anti-tumor drugs.
圆二色酸（RA，1）是一种天然化合物，具有很强的肿瘤细胞生长抑制作用。目前尚无关于 RA 衍生物的报道。此外，RA 的 28-COOH 位置可能使其在体内应用时不稳定，并引起严重的胃肠道副作用。因此，为了探索和利用这种化合物，我们在 RA 的 28-COOH 位置合成了 8 种新的氨基酸衍生物，并在体外对三种肿瘤细胞系（A375、HepG2 和 NCI-H446）进行了细胞毒性评价。结果表明，一些新的氨基酸衍生物具有更强的细胞毒性。与 RA 处理相比，化合物 5a 在三种测试的人肿瘤细胞系中表现出最好的抑制活性，IC50 值均小于 10 μM。同时，化合物 6b 在 A375 细胞系上的细胞毒性明显高于 RA，与 HepG2 和 NCI-H446 细胞系上的 RA 几乎相同。因此，化合物 5a 和 6b 可能成为开发新型抗肿瘤药物的潜在先导化合物。
