Design, Synthesis, and Evaluation of Benzoheterocyclic-Containing Derivatives as Novel HDAC1 Inhibitors

Abstract

In this study, the synthesis and biological evaluation of a variety of benzoheterocyclic-containing benzamide derivatives were described. Some of these compounds were proved to inhibiting the activity of histone deacetylase 1 (HDAC1) with IC₅₀ values below the micromolar range, retarding proliferation of several human cancer cells, and surprisingly, not possessing toxicity to human normal cells and hERG K⁺ ion channels. Among those compounds, 3c was the most potent and efficacious derivative. Compound 3c was orally active and displayed excellent in vivo antitumor activity in a HCT-116 xenograft mice model.

Keywords

benzamide derivatives - HDAC1 inhibitors - orally active - antitumor activity

Ethics Statement

The present study was approved by the animal ethics committee and abides by the relevant agreements of China State Institute of Pharmaceutical Industry, Shanghai, People's Republic of China.

Publication History

Received: 15 November 2021

Accepted: 29 January 2022

Article published online:
31 March 2022

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