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

• Main Authors: Matteo Incerti, Lucia Crascì, Paola Vicini, Esin Aki, Ismail Yalcin, Tugba Ertan-Bolelli, Venera Cardile, Adriana Carol Eleonora Graziano, Annamaria Panico
• Format: Article
• Language: English
• Published: MDPI AG 2018-02-01
• Series: Molecules
• Subjects: 4-thiazolidinones; ORAC assay; metalloproteinase-9; docking study; keratinocytes cultures; nuclear factor-κB
• Online Access: http://www.mdpi.com/1420-3049/23/2/415
• ISSN: 1420-3049

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).