Design, synthesis and biological evaluation of saccharin-based HDACs inhibitors for the treatment of triple-negative breast cancer
10.16438/j.0513-4870.2024-0562
- VernacularTitle:邻苯甲酰磺酰亚胺类HDACs抑制剂的设计、合成及抗三阴性乳腺癌活性研究
- Author:
Xiao-meng LI
1
;
Meng-yao QUAN
2
;
Yu-chen LIU
2
;
Xu-ben HOU
2
;
Lei-qiang HAN
1
;
Hao FANG
2
Author Information
1. Department of Pharmacy, the Second Hospital of Shandong University, Ji′nan
2. School of Pharmaceutical Science, Key Laboratory of Chemical Biology (Ministry of Education), Shandong University, Ji′nan
- Publication Type:Research Article
- Keywords:
saccharin;
histone deacetylase inhibitor;
anti-tumor;
triple-negative breast cancer;
structure-activity relationship
- From:
Acta Pharmaceutica Sinica
2024;59(11):3017-3026
- CountryChina
- Language:Chinese
-
Abstract:
As a key epigenetic regulator, histone deacetylases (HDACs) play a crucial role in cancer development. Small molecule HDAC inhibitors have been shown to inhibit tumor proliferation and induce apoptosis, attracting significant research attention. In this study, we designed and synthesized a series of novel saccharin derivatives as HDAC inhibitors. Biological experiments demonstrated that the target compound 9a exhibited superior HDACs inhibition activity to vorinostat and demonstrating promising in vitro and in vivo anti-tumor activity against triple-negative breast cancer (TNBC). All animal experiments in this study were performed in strict accordance with the protocols approved by the Ethical Committee of School of Pharmaceutical Sciences in Shandong University (Approval No. 230094). This work represents an initial exploration of developing saccharin-based HDAC inhibitors, and the active compound 9a could serve as a lead compound for further study.
