Design, Synthesis and Biological Evaluation of New HDAC1 and HDAC2 Inhibitors Endowed with Ligustrazine as a Novel Cap Moiety.

ABSTRACT:

Introduction

Histone deacetylases (HDACs) represent one of the most validated cancer targets. The inhibition of HDACs has been proven to be a successful strategy for the development of novel anticancer candidates.

Methods

This work describes design and synthesis of a new set of HDAC inhibitors (7a-c and 8a, b) utilizing ligustrazine as a novel cap moiety, and achieving the pharmacophoric features required to induce the desired inhibition.

Results

The newly synthesized derivatives were evaluated for their potential inhibitory activity toward two class I histone deacetylases, namely HDAC1 and HDAC2. The tested ligustrazine-based compounds were more potent toward HDAC2 (IC₅₀ range: 53.7-205.4 nM) than HDAC1 (IC₅₀ range: 114.3-2434.7 nM

SUBMITTER: Al-Sanea MM 

PROVIDER: S-EPMC7008064 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature