Antifibrotic and anticancer action of 5-ene amino/iminothiazolidinones

D. Kaminskyy, G.J. den Hartog, M. Wojtyra, M. Lelyukh, A. Gzella, A. Bast, R. Lesyk

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Pages (from-to)180-195
Number of pages16
JournalEuropean Journal of Medicinal Chemistry
Volume112
DOIs
Publication statusPublished - 13 Apr 2016

Keywords

  • Amino/amino-thiazolidinones
  • Synthesis
  • One-pot method
  • Antifibrotic activity
  • Superoxide radicals
  • Antiproliferative effects
  • IDIOPATHIC PULMONARY-FIBROSIS
  • CANCER CELL-LINES
  • MEDICINAL CHEMISTRY
  • ANTIINFLAMMATORY AGENTS
  • ANTITUMOR-ACTIVITY
  • CRYSTAL-STRUCTURES
  • DRUG DISCOVERY
  • DERIVATIVES
  • 4-THIAZOLIDINONES
  • ANTIOXIDANTS

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