Design, synthesis, and biological evaluation of (2E)-(2-oxo-1, 2-dihydro-3H-indol-3-ylidene)acetate derivatives as anti-proliferative agents through ROS-induced cell apoptosis
Design, synthesis, and biological evaluation of (2E)-(2-oxo-1, 2-dihydro-3H-indol-3-ylidene)acetate derivatives as anti-proliferative agents through ROS-induced cell apoptosis
复制标题
(2E)-(2-oxo-1, 2-diHydro-3H-indol-3-ylidene)acetate 衍生物的设计、合成和生物学评价作为通过 ROS 诱导细胞凋亡的抗增殖剂
DOI：
10.1016/j.ejmech.2016.09.005
复制
发表时间：
2016
影响因子：
6.7
通讯作者：
Yuan Haoliang
中科院分区：
文献类型：
--
作者：
Song Zhuang;Chen Cai-Ping;Liu Jun;Wen Xiaoan;Sun Hongbin;Yuan Haoliang
设计并合成了一类新的（2 E）-（2-氧代-1，2-二氢-3H-吲哚-3-亚基）乙酸酯衍生物作为有效的抗增殖剂。这些化合物对SK-BR-3、MDA-MB-231、HCT-116、SW 480、Ovcar-3、HL-60、Saos-2和HepG 2等肿瘤细胞株均表现出较强的抗增殖活性。化合物8和11 h被鉴定为最有效的化合物，而HL-60、HCT 116和MDA-MB-231是最敏感的细胞系。作用机制研究表明，化合物8通过抑制TrxR增加活性氧水平，进而通过激活凋亡蛋白bax和c-caspase 3诱导HCT 116细胞凋亡。初步的SAR分析表明，双键和酯基的修饰对化合物的抗增殖活性影响较大。本研究结果表明，（2 E）-（2-氧代-1，2-二氢-3H-吲哚-3-亚基）乙酸酯的抗肿瘤活性值得进一步研究。
A novel class of (2E)-(2-oxo-1, 2-dihydro-3H-indol-3-ylidene)acetate derivatives were designed and synthesized as potent anti-proliferative agents. Most of these compounds showed potent anti-proliferative activity against some tumor cell lines, including SK-BR-3, MDA-MB-231, HCT-116, SW480, Ovcar-3, HL-60, Saos-2 and HepG2. Compounds8cand11hwere identified as the most potent ones, while HL-60, HCT116 and MDA-MB-231 were the most sensitive cell lines. Mechanistic study revealed that compound8cenhanced reactive oxygen species level by inhibiting TrxR and then induced apoptosis by activating apoptosis proteins, bax and cleaved-caspase 3 in HCT116 cells. Preliminary SAR analysis indicated that modifications of the double bond and ester group made great effects on the anti-proliferative activity. Our findings suggested that it was worth further studies on the antitumor potency of (2E)-(2-oxo-1, 2-dihydro-3H-indol-3-ylidene)acetates.