Design, synthesis and anti-tumor activity evaluation of quinoline derivatives as histone deacetylase 8 inhibitors
10.16438/j.0513-4870.2023-0523
- VernacularTitle:喹啉类HDAC8选择性抑制剂的设计、合成及抗肿瘤活性研究
- Author:
Yi ZHOU
1
;
Wen-qing SHAO
1
;
Xin-ying YANG
2
;
Xu-ben HOU
2
;
Hao FANG
2
Author Information
1. Department of Pharmacy, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Ji'nan 250021, China
2. Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Science, Cheeloo College of Medicine, Shandong University, Ji'nan 250012, China
- Publication Type:Research Article
- Keywords:
quinoline derivative;
histone deacetylase 8 inhibitor;
anti-tumor activity;
pharmacophore model
- From:
Acta Pharmaceutica Sinica
2024;59(4):979-986
- CountryChina
- Language:Chinese
-
Abstract:
As a member of class I histone deacetylase (HDACs), HDAC8 is an important anticancer drug target. Based on our previously developed pharmacophore model for the HDAC8 inhibitor, we designed and synthesized 13 quinoline acid derivatives as new HDAC8 inhibitors. Among them, the compound SDFZ-E2 and SDFZ-E3 exhibited good HDAC8 inhibitory activities and isoform selectivity. In cell experiments, the target compounds SDFZ-E2 and SDFZ-E3 showed better antiproliferation activities than the known HDAC8 selective inhibitor PCI-34051. In addition, the proposed binding mode of SDFZ-E2 was investigated using molecular docking and molecular dynamics simulation. This work is a new attempt to develop HDAC8 selective inhibitor using quinoline as the scaffold, and the active compounds could serve as lead compounds for further structural optimization.
