School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
Bioorg Chem. 2020 May;98:103763. doi: 10.1016/j.bioorg.2020.103763. Epub 2020 Mar 14.
Thirteen new jatrophane diterpenoids, euphoresulanes A-M (1-13), and seven known analogues (14-20) were isolated from the whole plants of Euphorbia esula. Their structures were elucidated by extensive spectroscopic analysis, and the absolute configurations of 1, 6, and 10 were confirmed by single crystal X-ray diffraction. Compounds 1-20 were screened for the multidrug resistance (MDR) reversal activity on P-glycoprotein (Pgp)-dependent cancer cell line HepG2/ADR, and 1, 2, 4, 6, and 8 exhibited comparable activity to the positive drugs. Euphoresulane H (8), the most active MDR modulator, could enhance the efficacy of anticancer drug adriamycin to ca. 33 folds at 5 μM. The structure-activity relationship (SAR) study revealed that the acyloxy substitution at C-9 is essential to the activity and presence of H-2 was favorable.
从Euphorbia esula 的全株植物中分离得到了 13 种新的 Jatrophane 二萜类化合物， euphoresulanes A-M（1-13）和 7 种已知类似物（14-20）。通过广泛的光谱分析阐明了它们的结构，并通过单晶 X 射线衍射确定了 1、6 和 10 的绝对构型。对化合物 1-20 进行了多药耐药（MDR）逆转活性筛选，以 P-糖蛋白（Pgp）依赖性癌细胞系 HepG2/ADR 为靶点，化合物 1、2、4、6 和 8 与阳性药物具有相当的活性。Euphoresulane H（8）是最有效的 MDR 调节剂，在 5 μM 时可将抗癌药物阿霉素的疗效增强约 33 倍。构效关系（SAR）研究表明，C-9 位的酰氧基取代对于活性是必需的，而 H-2 的存在是有利的。
