{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T17:47:59Z","timestamp":1790272079112,"version":"4.1.0"},"reference-count":58,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2019,2,19]],"date-time":"2019-02-19T00:00:00Z","timestamp":1550534400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002848","name":"Comisi\u00f3n Nacional de Investigaci\u00f3n Cient\u00edfica y Tecnol\u00f3gica","doi-asserted-by":"publisher","award":["21140371 to Viviana Pardo Jim\u00e9nez"],"award-info":[{"award-number":["21140371 to Viviana Pardo Jim\u00e9nez"]}],"id":[{"id":"10.13039\/501100002848","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002848","name":"Comisi\u00f3n Nacional de Investigaci\u00f3n Cient\u00edfica y Tecnol\u00f3gica","doi-asserted-by":"publisher","award":["FONDECYT Grant N\u00b0 1130300 and N\u00b0 1170425"],"award-info":[{"award-number":["FONDECYT Grant N\u00b0 1130300 and N\u00b0 1170425"]}],"id":[{"id":"10.13039\/501100002848","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>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 \u03b1-SMA and procollagen I. In conclusion, the new thiazolyl-coumarin derivatives inhibit HDAC activity and decrease profibrotic effects on cardiac fibroblasts.<\/jats:p>","DOI":"10.3390\/molecules24040739","type":"journal-article","created":{"date-parts":[[2019,2,20]],"date-time":"2019-02-20T03:05:52Z","timestamp":1550631952000},"page":"739","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Synthesis and Biological Evaluation of Novel Thiazolyl-Coumarin Derivatives as Potent Histone Deacetylase Inhibitors with Antifibrotic Activity"],"prefix":"10.3390","volume":"24","author":[{"given":"Viviana","family":"Pardo-Jim\u00e9nez","sequence":"first","affiliation":[{"name":"Laboratory of Advanced Organic Chemistry, Department of Organic Chemistry and Physical Chemistry, Faculty of Chemical and Pharmaceutical Sciences; University of Chile, Santiago 8380000, Chile"},{"name":"Laboratory of Molecular Pharmacology, Department of Pharmacological &amp; Toxicological Chemistry, Faculty of Chemical and Pharmaceutical Sciences; University of Chile, Santiago 8380000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricio","family":"Navarrete-Encina","sequence":"additional","affiliation":[{"name":"Laboratory of Advanced Organic Chemistry, Department of Organic Chemistry and Physical Chemistry, Faculty of Chemical and Pharmaceutical Sciences; University of Chile, Santiago 8380000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillermo","family":"D\u00edaz-Araya","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Pharmacology, Department of Pharmacological &amp; Toxicological Chemistry, Faculty of Chemical and Pharmaceutical Sciences; University of Chile, Santiago 8380000, Chile"},{"name":"Advanced Center of Chronic Diseases (ACCDiS), Faculty of Chemical and Pharmaceutical Sciences, University of Chile, Santiago 8380000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,2,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2029","DOI":"10.1016\/j.jacc.2008.09.012","article-title":"Fibrosis: A living tissue and the infarcted heart","volume":"52","author":"Weber","year":"2008","journal-title":"J. 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