Design and synthesis of novel monoterpenoid indole alkaloid-like analogues and their antitumour activities in vitro
Design and synthesis of novel monoterpenoid indole alkaloid-like analogues and their antitumour activities in vitro
复制标题
新型单萜吲哚生物碱类似物的设计合成及其体外抗肿瘤活性
DOI：
10.1039/c8ob00677f
复制
发表时间：
2018-04-28
影响因子：
3.2
通讯作者：
Mu, Shuzhen
中科院分区：
文献类型：
--
作者：
Fang, Jiaqi;Huang, Tao;Mu, Shuzhen
采用仿生合成方法和组合化学方法合成了34个新的吲哚类单萜生物碱（MIA）类似物，并研究了它们对5种肿瘤细胞的细胞毒活性（SW-480、A-549、HL-60、SMMC-7721和MCF-7）使用3-（4，5-二甲基噻唑-2-基）-5-（3-羧基甲氧基苯基）-2-（4-磺基苯基）-2H-四唑鎓（MTS）测定。这些类似物中的14种（7、16-18和23-32）显示出比顺铂显著更大的肿瘤细胞增殖抑制。化合物17和18对HL-60细胞系显示出最高的细胞毒活性，其IC 50值分别为0.90 μ M和0.43 μ M。化合物18在SW-480、A-549、HL-60、SMMC-7721和MCF-7细胞中轻微诱导凋亡并阻滞细胞周期。一级构效关系的分析表明，在吲哚部分的C-3，C-5和C-6位置和京尼平部分的C-10位置处引入不同的取代基可能对所得化合物的抗肿瘤活性产生影响。
A biomimetic synthetic strategy and combinatorial chemistry were used to synthesize 34 novel mono-terpenoid indole alkaloid (MIA) analogues, and their cytotoxic activities against five cancer cell lines (SW-480, A-549, HL-60, SMMC-7721, and MCF-7) were determined using the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay. Fourteen of these analogues (7, 16-18, and 23-32) showed significantly greater inhibition of tumour cell proliferation than cisplatin. Compounds 17 and 18 showed the highest cytotoxic activity against the HL-60 cell line with IC50 values of 0.90 mu M and 0.43 mu M, respectively. Compound 18 slightly induced apoptosis and arrested the cell cycle in SW-480, A-549, HL-60, SMMC-7721, and MCF-7 cells. Analysis of the primary structure-activity relationships reveals that the introduction of different substituent groups at the C-3, C-5, and C-6 positions of the indole moiety and the C-10 position of the genipin moiety might have an effect on the antitumour activity of the resulting compounds.