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

Matteo Incerti; Lucia Crascì; Paola Vicini; Esin Aki; Ismail Yalcin; Tugba Ertan-Bolelli; Venera Cardile; Adriana Carol Eleonora Graziano; Annamaria Panico

doi:10.3390/molecules23020415

Molecules (Feb 2018)

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

Matteo Incerti,
Lucia Crascì,
Paola Vicini,
Esin Aki,
Ismail Yalcin,
Tugba Ertan-Bolelli,
Venera Cardile,
Adriana Carol Eleonora Graziano,
Annamaria Panico

Affiliations

Matteo Incerti: Department of Food and Drug, University of Parma, Parco Area delle Scienze 27/A, 43124 Parma, Italy
Lucia Crascì: Department of Drug Sciences, University of Catania, V. le A. Doria 6, 95125 Catania, Italy
Paola Vicini: Department of Food and Drug, University of Parma, Parco Area delle Scienze 27/A, 43124 Parma, Italy
Esin Aki: Pharmaceutical Chemistry Department, Faculty of Pharmacy, Ankara University, Tandogan, Ankara 06100, Turkey
Ismail Yalcin: Pharmaceutical Chemistry Department, Faculty of Pharmacy, Ankara University, Tandogan, Ankara 06100, Turkey
Tugba Ertan-Bolelli: Pharmaceutical Chemistry Department, Faculty of Pharmacy, Ankara University, Tandogan, Ankara 06100, Turkey
Venera Cardile: Department of Physiological Sciences, University of Catania, V. le A. Doria 6, 95125 Catania, Italy
Adriana Carol Eleonora Graziano: Department of Physiological Sciences, University of Catania, V. le A. Doria 6, 95125 Catania, Italy
Annamaria Panico: Department of Drug Sciences, University of Catania, V. le A. Doria 6, 95125 Catania, Italy

DOI: https://doi.org/10.3390/molecules23020415
Journal volume & issue: Vol. 23, no. 2
p. 415

Abstract

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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(IC50 = 40 nM).

Published in Molecules

ISSN: 1420-3049 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Science: Chemistry: Organic chemistry
Website: http://www.mdpi.com/journal/molecules

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