Modeling and biological evaluation of 3,3′-(1,2-ethanediyl)bis[2-(4-methoxyphenyl)-thiazolidin-4-one], a new synthetic cyclooxygenase-2 inhibitor
| Autor: | F. Monforte, Grazia De Luca, Stefano Alcaro, Laura Dugo, Lidia Sautebin, Emanuela Mazzon, Francesco Ortuso, Rosanna Maccari, Achille P. Caputi, Salvatore Cuzzocrea, Rosaria Ottanà, Maria Gabriella Vigorita |
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| Rok vydání: | 2002 |
| Předmět: |
Male
Stereochemistry Lung injury Carrageenan Stereocenter Rats Sprague-Dawley chemistry.chemical_compound In vivo Animals Humans Cyclooxygenase Inhibitors Pleurisy chemical modeling Pharmacology biology Chemistry Aryl Biological activity cyclooxygenase-2 carrageenan-induced pleurisy In vitro Rats Thiazoles Enzyme inhibitor biology.protein Thiazolidines Lead compound |
| Zdroj: | European Journal of Pharmacology. 448:71-80 |
| ISSN: | 0014-2999 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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