Antifibrotic and anticancer action of 5-ene amino/iminothiazolidinones

Eur J Med Chem. 2016 Apr 13:112:180-195. doi: 10.1016/j.ejmech.2016.02.011. Epub 2016 Feb 9.

Abstract

Here we describe the synthesis and the antifibrotic and anticancer activity determination of amino(imino)thiazolidinone derivatives. An efficient one-pot three-component reaction which involved [2 + 3]-cyclocondensation and Knoevenagel condensation was used for the synthesis of 5-ene-2-amino(imino)-4-thiazolidinones. Following amino-imino tautomerism, the compound structures were confirmed by X-ray analysis. Comparison of SRB assays on fibroblasts and cancer cells revealed that compounds which significantly reduced the viability of fibroblasts did not possess an anticancer effect. A series of thiazolidinone derivatives as interesting candidates for further testing has been identified. Among the tested compounds 2-{3-furan-2-ylmethyl-2-[(2-methyl-3-phenylallylidene)hydrazono]-thiazolidin-4-one-5-yl}-N-(3-trifluoromethylphenyl)-acetamide (5), N-(2-methoxyphenyl)-2-[5-(4-oxothiazolidin-2-ylideneamino)-[1,3,4]thiadiazol-2-ylsulfanyl]-acetamide (12), 3-[3-allyl-4-oxo-2-(thiazol-2-ylimino)thiazolidin-5-ylidene]-1,3-dihydroindol-2-one (33), and 5(Z)-(thiophen-2-ylmethylene)-4-(4-chlorophenylamino)thiazol-2(5H)-one (34) possessed high antifibrotic activity levels, had a similar effect as Pirfenidone, and did not scavenge superoxide radicals. Their antifibrotic potential was confirmed using the xCelligence system.

Keywords: Amino/amino-thiazolidinones; Antifibrotic activity; Antiproliferative effects; One-pot method; Superoxide radicals; Synthesis.

MeSH terms

  • Amination
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology*
  • Cell Line
  • Cell Proliferation / drug effects*
  • Cell Survival / drug effects
  • Crystallography, X-Ray
  • Fibroblasts / cytology
  • Fibroblasts / drug effects*
  • Fibroblasts / metabolism
  • Humans
  • Idiopathic Pulmonary Fibrosis / drug therapy
  • Idiopathic Pulmonary Fibrosis / metabolism
  • Imines / chemistry
  • Imines / pharmacology
  • Lung / cytology
  • Lung / drug effects
  • Lung / metabolism
  • Models, Molecular
  • Superoxides / metabolism
  • Thiazolidines / chemistry*
  • Thiazolidines / pharmacology*

Substances

  • Antineoplastic Agents
  • Imines
  • Thiazolidines
  • Superoxides