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4-Thiazolidinone Derivatives as MMP Inhibitors in Tissue Damage: Synthesis, Biological Evaluation and Docking Studies

Nine 2-(1,2-benzothiazol-3-yl)-N-(4-oxo-2-phenyl-1,3-thiazolidin-3-yl)propanamides combining a benzisothiazole and 4-thiazolidinone in one framework were designed and synthesized. The aim of the study was to verify their effectiveness to affect the inflammatory/oxidative process in which free oxygen...

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Autores principales: Incerti, Matteo, Crascì, Lucia, Vicini, Paola, Aki, Esin, Yalcin, Ismail, Ertan-Bolelli, Tugba, Cardile, Venera, Graziano, Adriana Carol Eleonora, Panico, Annamaria
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6017844/
https://www.ncbi.nlm.nih.gov/pubmed/29443898
http://dx.doi.org/10.3390/molecules23020415
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author Incerti, Matteo
Crascì, Lucia
Vicini, Paola
Aki, Esin
Yalcin, Ismail
Ertan-Bolelli, Tugba
Cardile, Venera
Graziano, Adriana Carol Eleonora
Panico, Annamaria
author_facet Incerti, Matteo
Crascì, Lucia
Vicini, Paola
Aki, Esin
Yalcin, Ismail
Ertan-Bolelli, Tugba
Cardile, Venera
Graziano, Adriana Carol Eleonora
Panico, Annamaria
author_sort Incerti, Matteo
collection PubMed
description Nine 2-(1,2-benzothiazol-3-yl)-N-(4-oxo-2-phenyl-1,3-thiazolidin-3-yl)propanamides combining a benzisothiazole and 4-thiazolidinone in one framework were designed and synthesized. The aim of the study was to verify their effectiveness to affect the inflammatory/oxidative process in which free oxygen and nitrite (ROS and RNS) radicals, inflammatory mediators, such as nuclear factor κB (NF-κB), and matrix metalloproteinases (MMPs) are involved. Docking studies of all the compounds were performed in order to explore their binding mode at the MMP-9 protein. An appreciable anti-inflammatory/potential wound healing effects of the tested compounds was highlighted. Derivative 23, bearing a 4-carboxyphenyl substituent at C2 of the 4-thiazolidinone ring, exhibited the highest activity, being able to inhibit MMP-9 at nanomolar level(IC(50) = 40 nM).
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spelling pubmed-60178442018-11-13 4-Thiazolidinone Derivatives as MMP Inhibitors in Tissue Damage: Synthesis, Biological Evaluation and Docking Studies Incerti, Matteo Crascì, Lucia Vicini, Paola Aki, Esin Yalcin, Ismail Ertan-Bolelli, Tugba Cardile, Venera Graziano, Adriana Carol Eleonora Panico, Annamaria Molecules Article Nine 2-(1,2-benzothiazol-3-yl)-N-(4-oxo-2-phenyl-1,3-thiazolidin-3-yl)propanamides combining a benzisothiazole and 4-thiazolidinone in one framework were designed and synthesized. The aim of the study was to verify their effectiveness to affect the inflammatory/oxidative process in which free oxygen and nitrite (ROS and RNS) radicals, inflammatory mediators, such as nuclear factor κB (NF-κB), and matrix metalloproteinases (MMPs) are involved. Docking studies of all the compounds were performed in order to explore their binding mode at the MMP-9 protein. An appreciable anti-inflammatory/potential wound healing effects of the tested compounds was highlighted. Derivative 23, bearing a 4-carboxyphenyl substituent at C2 of the 4-thiazolidinone ring, exhibited the highest activity, being able to inhibit MMP-9 at nanomolar level(IC(50) = 40 nM). MDPI 2018-02-14 /pmc/articles/PMC6017844/ /pubmed/29443898 http://dx.doi.org/10.3390/molecules23020415 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Incerti, Matteo
Crascì, Lucia
Vicini, Paola
Aki, Esin
Yalcin, Ismail
Ertan-Bolelli, Tugba
Cardile, Venera
Graziano, Adriana Carol Eleonora
Panico, Annamaria
4-Thiazolidinone Derivatives as MMP Inhibitors in Tissue Damage: Synthesis, Biological Evaluation and Docking Studies
title 4-Thiazolidinone Derivatives as MMP Inhibitors in Tissue Damage: Synthesis, Biological Evaluation and Docking Studies
title_full 4-Thiazolidinone Derivatives as MMP Inhibitors in Tissue Damage: Synthesis, Biological Evaluation and Docking Studies
title_fullStr 4-Thiazolidinone Derivatives as MMP Inhibitors in Tissue Damage: Synthesis, Biological Evaluation and Docking Studies
title_full_unstemmed 4-Thiazolidinone Derivatives as MMP Inhibitors in Tissue Damage: Synthesis, Biological Evaluation and Docking Studies
title_short 4-Thiazolidinone Derivatives as MMP Inhibitors in Tissue Damage: Synthesis, Biological Evaluation and Docking Studies
title_sort 4-thiazolidinone derivatives as mmp inhibitors in tissue damage: synthesis, biological evaluation and docking studies
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6017844/
https://www.ncbi.nlm.nih.gov/pubmed/29443898
http://dx.doi.org/10.3390/molecules23020415
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