State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, 3491 Baijin Road, Guiyang 550014, PR China.
Org Biomol Chem. 2018 Apr 25;16(16):3026-3037. doi: 10.1039/c8ob00677f.
A biomimetic synthetic strategy and combinatorial chemistry were used to synthesize 34 novel monoterpenoid 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 μM and 0.43 μM, 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.
采用仿生合成策略和组合化学方法合成了 34 种新型单萜吲哚生物碱（MIA）类似物，并采用 3-(4,5-二甲基噻唑-2-基）-5-(3-羧甲氧苯基）-2-(4-磺苯基）-2H-四唑（MTS）法测定了它们对五种癌细胞系（SW-480、A-549、HL-60、SMMC-7721 和 MCF-7）的细胞毒性。其中 14 种类似物（7、16-18 和 23-32）对肿瘤细胞增殖的抑制作用明显强于顺铂。化合物 17 和 18 对 HL-60 细胞系的细胞毒性最高，IC50 值分别为 0.90 μM 和 0.43 μM。化合物 18 轻微诱导 SW-480、A-549、HL-60、SMMC-7721 和 MCF-7 细胞凋亡并阻滞细胞周期。对原始结构-活性关系的分析表明，吲哚部分的 C-3、C-5 和 C-6 位以及京尼平部分的 C-10 位引入不同取代基可能对所得化合物的抗肿瘤活性有影响。
