New quaternary ammonium oxicam derivatives: synthesis and in vitro antiosteoarthritis evaluation.
A series of new oxicam derivatives bearing a quaternary ammonium (QA) moiety was synthesized and evaluated in vitro for antiosteoarthritis properties. Propyltrimethyl ammonium 3 and propyldiethylmethyl ammonium 11 stimulated aggrecan expression and mitigated the inhibitory action of IL-1. QA derivative 3 also increased TGF-beta2 and type II receptor expression. These results suggest that such derivatives may not only inhibit the osteoarthritis degradation process but also stimulate its regeneration. QA derivatives 3 and 11 offer potential for developing new therapeutic approaches to osteoarthritis treatment.
Vidal
Aurélien
A
UMR 990 INSERM/Université d'Auvergne, BP 184, 63005 Clermont-Ferrand Cedex, France. aurelien.vidal@inserm.fr
Chezal
Jean-Michel
JM
Mounetou
Emmanuelle
E
D053674:Aggrecans / Q000235:genetics; D000818:Animals; D002358:Cartilage, Articular / Q000187:drug effects / Q000473:pathology; D002417:Cattle; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D010003:Osteoarthritis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000644:Quaternary Ammonium Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics
D053674:Aggrecans; D000644:Quaternary Ammonium Compounds; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta