Synthesis and Biological Evaluation of Novel Thiazolyl-Coumarin Derivatives As Potent Histone Deacetylase Inhibitors with Antifibrotic Activity

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2019 Feb 23

PMID 30791388

Citations 7

Authors

Viviana Pardo-Jimenez

Patricio Navarrete-Encina

Guillermo Diaz-Araya

Affiliations

Soon will be listed here.

Abstract

New histone deacetylases (HDAC) inhibitors with low toxicity to non-cancerous cells, are a prevalent issue at present because these enzymes are actively involved in fibrotic diseases. We designed and synthesized a novel series of thiazolyl-coumarins, substituted at position 6 (R = H, Br, OCH₃), linked to classic zinc binding groups, such as hydroxamic and carboxylic acid moieties and alternative zinc binding groups such as disulfide and catechol. Their in vitro inhibitory activities against HDACs were evaluated. Disulfide and hydroxamic acid derivatives were the most potent ones. Assays with neonatal rat cardiac fibroblasts demonstrated low cytotoxic effects for all compounds. Regarding the parameters associated to cardiac fibrosis development, the compounds showed antiproliferative effects, and triggered a strong decrease on the expression levels of both α-SMA and procollagen I. In conclusion, the new thiazolyl-coumarin derivatives inhibit HDAC activity and decrease profibrotic effects on cardiac fibroblasts.

Citing Articles

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