State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Bioactive Natural Product Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China.
Molecules. 2021 Mar 4;26(5):1380. doi: 10.3390/molecules26051380.
Harringtonolide (HO), a natural product isolated from , exhibits potent antiproliferative activity. However, little information has been reported on the systematic structure-activity relationship (SAR) of HO derivatives. Modifications on tropone, lactone, and allyl positions of HO () were carried out to provide 17 derivatives (--). The in vitro antiproliferative activity against four cancer cell lines (HCT-116, A375, A549, and Huh-7) and one normal cell line (L-02) was tested. Amongst these novel derivatives, compound exhibited comparable cell growth inhibitory activity to HO and displayed better selectivity index (SI = 56.5) between Huh-7 and L-02 cells. The SAR results revealed that the tropone and lactone moieties are essential for the cytotoxic activities, which provided useful suggestions for further structural optimization of HO.
从 中分离得到的天然产物诃黎酮（HO）具有很强的抗增殖活性。然而，关于 HO 衍生物的系统结构-活性关系（SAR）的信息却很少。对诃黎酮（）的三酮、内酯和烯丙基位置进行修饰，得到了 17 个衍生物（--）。对这 4 种癌细胞系（HCT-116、A375、A549 和 Huh-7）和 1 种正常细胞系（L-02）进行了体外抗增殖活性测试。在这些新型衍生物中，化合物 对细胞生长的抑制活性与 HO 相当，并且在 Huh-7 和 L-02 细胞之间显示出更好的选择性指数（SI = 56.5）。SAR 结果表明，三酮和内酯部分是细胞毒性活性所必需的，这为 HO 的进一步结构优化提供了有用的建议。
