Ring size changes in the development of class I HDAC inhibitors

Er-Chieh Cho; Chi-Yuan Liu; Di-Wei Tang; Hsueh-Yun Lee

doi:10.1080/14756366.2021.1941920

Ring size changes in the development of class I HDAC inhibitors

J Enzyme Inhib Med Chem. 2021 Dec;36(1):1387-1401. doi: 10.1080/14756366.2021.1941920.

Authors

Er-Chieh Cho^{1

2

3}, Chi-Yuan Liu¹, Di-Wei Tang¹, Hsueh-Yun Lee^{1

4}

Affiliations

¹ School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan.
² Master Program in Clinical Genomics and Proteomics, College of Pharmacy, Taipei Medical University, Taipei, Taiwan.
³ Cancer Center, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
⁴ Ph.D. Program in Drug Discovery and Development Industry, College of Pharmacy, Taipei Medical University, Taipei, Taiwan.

Abstract

Five pathways involving different ring structures led to generation of fourteen thienylbenzamides (7-20) which display the structure-activity relationships of class I HDAC inhibitors. All the synthesised compounds inhibit HDAC1 and HDAC2 selectively over other isoforms and many inhibit DLD1 and HCT116 cells more effectively than a parent compound. Compounds 8 and 16 inhibit HCT116 cells by activation of the apoptosis pathway.

Keywords: HDAC; Thienylbenzamides; colon cancer; ring transformation.

MeSH terms

Apoptosis / drug effects
Cell Proliferation / drug effects
Drug Development*
HCT116 Cells
Histone Deacetylase Inhibitors / chemistry*
Histone Deacetylase Inhibitors / pharmacology
Humans
Molecular Structure
Structure-Activity Relationship

Substances

Histone Deacetylase Inhibitors

Grants and funding

This research was supported by the Ministry of Science and Technology, Taiwan [grant no. MOST108-2320-B-038-042-MY3 and MOST 109-2320-B-038-038], Taiwan, and WanFang Hospital, Chi-Mei Medical Center, and Hualien Tzu-Chi Hospital Joint Cancer Center Grant-Focus on Colon Cancer Research [MOHW109-TDU-B-212-134020, supported by Health and welfare surcharge of tobacco products], Taiwan.