Design, synthesis and anticancer activity studies of novel indole derivatives as Bcl-2/Mcl-1 dual inhibitors

被引：7

作者：

Liu, Yingfei ^{[1
]}

Li, Jianjun ^{[1
]}

Zhou, Guanghui ^{[1
]}

Zhang, Jiale ^{[1
]}

Teng, Yu ^{[1
]}

Bai, Zhushuang ^{[2
]}

Liu, Tingting ^{[1
]}

机构：

[1] Shandong First Med Univ & Shandong Acad Med Sci, Sch Pharm, Dept Med Chem, Tai An 271016, Shandong, Peoples R China

[2] Shandong First Med Univ & Shandong Acad Med Sci, Inst Mat Med, Jinan 250000, Shandong, Peoples R China

来源：

MEDICINAL CHEMISTRY RESEARCH | 2023年 / 32卷 / 01期

基金：

中国国家自然科学基金;

关键词：

Indole; Bcl-2; Mcl-1; Antitumor; Inhibitory activity; SCAFFOLD;

D O I：

10.1007/s00044-022-02991-y

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of novel indole derivatives were designed, synthesized and evaluated for the binding affinity of Bcl-2 family proteins and antiproliferative activity against three selected cancer cell lines (PC-3, Jurkat, and MDA-MB-231). The preliminary structure-activity relationship (SAR) for this indole scaffold was summarized. Among all the compounds, compound 9k showed the best inhibitory activity against Bcl-2 and Mcl-1 proteins with IC50 values of 7.63 mu M and 1.53 mu M, respectively, which is comparable to the positive control AT-101. The docking study of it with Bcl-2 and Mcl-1 proteins indicated that it could bind to the active pocket of them through Van der Waals forces, hydrogen bond, etc. However, the three compounds with good binding affinity of Bcl-2 protein exhibited weaker antitumor activity compared to AT-101, which need further modification.

引用

页码：99 / 108

页数：10

共 17 条

[1] Development of the pan-DAC inhibitor panobinostat (LBH589): Successes and challenges [J].