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

Molecules. 2018 Feb 14;23(2):415. doi: 10.3390/molecules23020415.

Abstract

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).

Keywords: 4-thiazolidinones; ORAC assay; docking study; keratinocytes cultures; metalloproteinase-9; nuclear factor-κB.

MeSH terms

  • Humans
  • Inflammation / drug therapy*
  • Inflammation / metabolism
  • Matrix Metalloproteinase 9 / chemistry
  • Matrix Metalloproteinase 9 / drug effects
  • Matrix Metalloproteinase Inhibitors / chemical synthesis
  • Matrix Metalloproteinase Inhibitors / chemistry*
  • Molecular Docking Simulation
  • NF-kappa B / metabolism
  • Propane / chemical synthesis
  • Propane / chemistry
  • Thiazolidines / chemical synthesis
  • Thiazolidines / chemistry*

Substances

  • 4-thiazolidinone
  • Matrix Metalloproteinase Inhibitors
  • NF-kappa B
  • Thiazolidines
  • Matrix Metalloproteinase 9
  • Propane