Modeling and biological evaluation of 3,3′-(1,2-ethanediyl)bis[2-(4-methoxyphenyl)-thiazolidin-4-one], a new synthetic cyclooxygenase-2 inhibitor

Rosaria Ottaná, Emanuela Mazzon, Laura Dugo, Francesca Monforte, Rosanna Maccari, Lidia Sautebin, Grazia De Luca, Maria Gabriella Vigorita, Stefano Alcaro, Francesco Ortuso, Achille P. Caputi, Salvatore Cuzzocrea

Research output: Contribution to journalArticlepeer-review

Abstract

Within the series of chiral 3,3′-(1,2-ethanediyl)bis[2-arylthiazolidin-4-ones], the 3,4-dimethoxyphenyl substituted derivative was found in the primary anti-inflammatory screening to be endowed with superior in vivo properties and good safety profile. Such a lead compound was modified by eliminating 3-methoxy group while retaining 4-methoxy group on the aryl rings at 2 and 2′ stereogenic carbons. The 2R,2′S-meso isomer (VIG3b) of the resulting bisthiazolidinone has been widely investigated. The inhibitory effects on cyclo-oxygenase-1 and cyclo-oxygenase-2 isoenzymes were measured in a human whole blood assay. VIG3b was almost 50 times more selective on the inducible isoform. The cyclo-oxygenase-2 preferential selectivity has been confirmed by modeling VIG3b into the cyclo-oxygenase-1 and cyclo-oxygenase-2 active sites. furthermore, VIG3b was assayed in the experimental model of carrageenan-induced lung injury by evaluating its ability to inhibit: (1) fluid accumulation in the pleural cavity, (2) neutrophil infiltration, (3) prostaglandin E2 production and (4) lung injury. VIG3b exhibited interesting activity in all these tests.

Original languageEnglish
Pages (from-to)71-80
Number of pages10
JournalEuropean Journal of Pharmacology
Volume448
Issue number1
DOIs
Publication statusPublished - Jul 12 2002

Keywords

  • Carrageenan-induced pleurisy
  • Chemical modeling
  • Cyclooxygenase-2

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Fingerprint Dive into the research topics of 'Modeling and biological evaluation of 3,3′-(1,2-ethanediyl)bis[2-(4-methoxyphenyl)-thiazolidin-4-one], a new synthetic cyclooxygenase-2 inhibitor'. Together they form a unique fingerprint.

Cite this