Format

Send to

Choose Destination
Biosci Trends. 2019 Jul 22;13(3):267-272. doi: 10.5582/bst.2019.01054. Epub 2019 May 31.

Design and synthesis of novel histone deacetylase 6 inhibitors with benzyl-triazole as the core skeleton.

Author information

1
Department of Pharmacology, School of Pharmacy, Qingdao University.
2
Department of Medicinal Chemistry, School of Pharmacy, Qingdao University.

Abstract

In the field of epigenetics, histone deacetylases (HDACs) are important members and well validated targets for anti-cancer drugs discovery. In this study, we designed and synthesized twenty-seven novel hydroxamic acid-based HDAC inhibitors (HDACis) with benzyl-triazole as the core skeleton. Most target compounds displayed excellent inhibition rates toward HDACs. Among them, compounds ZM-22 to ZM-27 with inhibition rates more than 90% toward HDACs exhibited potent inhibitory activity toward HDAC6, and ZM-23 possessed the best selectivity to HDAC6 over HDAC1. The high potency of compound ZM-23 toward HDAC6 was rationalized by molecular docking simulation. This series of compounds is worthy for further anti-cancer activity evaluation and structural optimization works.

KEYWORDS:

Histone deacetylase; anti-tumor; inhibitor; isoform; selective

PMID:
31155552
DOI:
10.5582/bst.2019.01054
Free full text

Supplemental Content

Full text links

Icon for J-STAGE, Japan Science and Technology Information Aggregator, Electronic
Loading ...
Support Center