Semisynthesis and in vitro cytotoxic evaluation of new analogues of 1-O-acetylbritannilactone, a sesquiterpene from Inula britannica
Semisynthesis and in vitro cytotoxic evaluation of new analogues of 1-O-acetylbritannilactone, a sesquiterpene from Inula britannica
复制标题
DOI：
10.1016/j.ejmech.2014.04.028
复制
发表时间：
2014-06-10
影响因子：
6.7
通讯作者：
Gao, Jin-Ming
中科院分区：
文献类型：
--
作者：
Dong, Shuai;Tang, Jiang-Jiang;Gao, Jin-Ming
从药用植物旋覆花中分离得到一种倍半萜类化合物1-O-乙酰基旋覆花内酯（ABL），它的半合成类似物对人癌细胞株HCT 116、HEp-2、HeLa和正常仓鼠细胞株CHO等4种细胞株具有明显的体外细胞毒活性。构效关系表明，酯化6-OH（增强亲脂性）和α-亚甲基-γ-内酯功能发挥重要作用，赋予细胞毒性。在测试的化合物中，在6-OH位置带有月桂酰基（12 C）的14种显示出最有效的体外细胞毒性活性，IC 50值在2.91和6.78 μ M之间，与阳性对照依托泊苷（VP-16，IC 50值在2.13和4.79 μ M之间）相当。此外，化合物14在低浓度下引发显著的细胞凋亡，并诱导HCT 116细胞的细胞周期停滞在G2/M期。用正常细胞（CHO）进行的生物测定显示，所有合成化合物对测试的癌细胞系都没有选择性。(C)2014年Elsevier Masson SAS。All rights reserved.
Semisynthetic analogues of the natural product 1-O-acetylbritannilactone (ABL), a sesquiterpene isolated from the medicinal plant Inula britannica, have been prepared and exhibited significant in vitro cytotoxic activities against four cell lines including three human cancer cell lines (HCT116, HEp-2 and HeLa) and one normal hamster cell line (CHO). Structure activity relationships indicate that esterification of 6-OH (enhanced lipophilicity) and alpha-methylene-gamma-lactone functionalities play important roles in conferring cytotoxicity. Among the tested compounds, 14 bearing a lauroyl group (12C) at the 6-OH position displayed most potent in vitro cytotoxic activity, with IC50 values between 2.91 and 6.78 mu M, comparable to the positive control etoposide (VP-16, IC50 values between 2.13 and 4.79 mu M). Moreover, the compound 14 triggered remarkable apoptosis at a low concentration, and induced cell cycle arrest in G2/M phase in HCT116 cells. The biological assays conducted with normal cells (CHO) revealed that all the synthetic compounds are no selective against cancer cell lines tested. (C) 2014 Elsevier Masson SAS. All rights reserved.