Anti-inflammatory/analgesic 3,3'-(1,2-ethanediyl)-bis[2-(3,4-dimethoxyphenyl)-4-thiazolidinones] 1, obtained as racemic mixtures (a) and mesoforms (b), have two equivalent stereogenic centres (C-2 and C-2') and exist as RR, SS and RS isomers. The enantioseparation of 1a provided the single enantiomers that displayed different in vitro cyclooxygenase-1/cyclooxygenase-2 selectivity ratios. In particular the dextrorotatory compound is a highly selective COX-2 inhibitor and the levorotatory one is moderately selective. Instead, RS-meso isomer (1b) exhibited similar levels of inhibitory activity on both COX isozymes. The diastereo- and enantioselectivity has been explained by molecular modelling of RR, SS and RS compounds into COX-1 and COX-2 binding sites. Theoretical results indicated SS>RS>RR affinity order towards COX-2 isoenzyme, in agreement with in vitro and previous in vivo pharmacological results.

Chiral 3,3 '-(1,2-ethanediyl)-bis[2-(3,4-dimethoxyphenyl)-4- thiazolidinones] with anti-inflammatory activity. Part 11: Evaluation of COX-2 selectivity and modelling

VIGORITA, Maria;OTTANA', Rosaria;MACCARI, Rosanna;MONFORTE, Maria Teresa;TROVATO, Ada;TAVIANO, Maria Fernanda;MICELI, Natalizia;DE LUCA, Grazia;
2003-01-01

Abstract

Anti-inflammatory/analgesic 3,3'-(1,2-ethanediyl)-bis[2-(3,4-dimethoxyphenyl)-4-thiazolidinones] 1, obtained as racemic mixtures (a) and mesoforms (b), have two equivalent stereogenic centres (C-2 and C-2') and exist as RR, SS and RS isomers. The enantioseparation of 1a provided the single enantiomers that displayed different in vitro cyclooxygenase-1/cyclooxygenase-2 selectivity ratios. In particular the dextrorotatory compound is a highly selective COX-2 inhibitor and the levorotatory one is moderately selective. Instead, RS-meso isomer (1b) exhibited similar levels of inhibitory activity on both COX isozymes. The diastereo- and enantioselectivity has been explained by molecular modelling of RR, SS and RS compounds into COX-1 and COX-2 binding sites. Theoretical results indicated SS>RS>RR affinity order towards COX-2 isoenzyme, in agreement with in vitro and previous in vivo pharmacological results.
2003
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11570/1891706
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