5-Thioxoimidazolidine-2-one derivatives: Synthesis, anti-inflammatory activity, analgesic activity, COX inhibition assay and molecular modelling study

Marwa A.M.Sh El-Sharief, Samir Y. Abbas, Ahmed M.Sh El-Sharief, Nermien M. Sabry, Ziad Moussa, Shahenda M. El-Messery, Ahmed R. Elsheakh, Ghada S. Hassan, Mardia T. El Sayed

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

A series of 5-imino-4-thioxo-2-imidazolidinone derivatives with different substituents at N 1 and N 3 was synthesized with high yield and excellent purity by the reaction of different N-arylcyanothioformamide derivatives with isocyanate derivatives. Treatment 5-imino-4-thioxo-2-imidazolidinone derivatives with acidic medium afforded 4-thioxoimidazolidin-2,5-dione derivatives. The structures of the obtained products were established based on spectroscopic IR, 1 H NMR, 13 C NMR, 1 H, 1 H-COSY, HSQC and elemental analyses. The anti-inflammatory activity of the synthesized compounds through the carrageenan-paw edema model as well as in vitro COX-1 and COX-2 inhibition assay were evaluated where most of the synthesized compounds showed significant anti-inflammatory activity. Mostly, all of our synthesized compounds have greater activity more than celecoxib toward both cyclooxygenase enzymes. All of the tested compounds (except one compound) exhibited IC 50 valves for COX-2 ranged from 0.001 × 10 −3 to 0.827 × 10 −3 µM while the reference drug has IC 50 40.0 × 10 −3 µM. Furthermore, the analgesic activity of such compounds was also determined. Molecular modeling study was also conducted to rationalize the potential as anti-inflammatory agents of our synthesized compounds by predicting their binding modes, binding affinities and optimal orientation at the active site of the COX enzymes.

Original languageEnglish
Pages (from-to)679-687
Number of pages9
JournalBioorganic Chemistry
Volume87
DOIs
Publication statusPublished - Jun 2019

Keywords

  • Analgesic activity
  • Anti-inflammatory activity
  • COX inhibition assay
  • Imidazolidin-2,5-diones
  • Imidazolidineiminothiones
  • N-Arylcyanothioformamides

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Drug Discovery
  • Organic Chemistry

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