Evodiamine-inspired dual inhibitors of histone deacetylase 1 (HDAC1) and topoisomerase 2 (TOP2) with potent antitumor activity

• 作者: Chunquan Sheng Guoqiang Dong Shanchao Wu Shuqiang Chen Yahui Huang
• 来源期刊: 药学学报（英文版）
• 年，卷（期）: 2020,（7）
• 所属期刊栏目: Original Articles
• 页码范围: 1294-1308
• 页数: 15页
• 语种: 英文

摘要

A great challenge in multi-targeting drug discovery is to identify drug-like lead compounds with therapeutic advantages over single target inhibitors and drug combinations.Inspired by our previous efforts in designing antitumor evodiamine derivatives,herein selective histone deacetylase 1 (HDACl) and topoisomerase 2 (TOP2) dual inhibitors were successfully identified,which showed potent in vitro and in vivo antitumor potency.Particularly,compound 30a was orally active and possessed excellent in vivo antitumor activity in the HCT 116 xenograft model (TGI =75.2％,150 mg/kg,p.o.) without significant toxicity,which was more potent than HDAC inhibitor vorinostat,TOP inhibitor evodiamine and their combination.Taken together,this study highlights the therapeutic advantages of evodiamine-based HDAC 1/TOP2 dual inhibitors and provides valuable leads for the development of novel multi-targeting antitumor agents.

作者信息

序号	姓名	单位	发文数	被引次数	H指数	G指数
1	Yahui Huang		1	0	0.0	0.0
2	Shuqiang Chen		1	0	0.0	0.0
3	Shanchao Wu		1	0	0.0	0.0
4	Guoqiang Dong		1	0	0.0	0.0
5	Chunquan Sheng		1	0	0.0	0.0