title: Synthesis and in vitro evaluation of targeted tetracycline derivatives: effects on inhibition of matrix metalloproteinases.
abstract: Among other non-antibiotic properties, tetracyclines inhibit matrix metalloproteinases and are currently under study for the treatment of osteoarthritis. Quaternary ammonium conjugates of tetracyclines were synthesized by direct alkylation of the amine function at the 4-position with methyl iodide. When tested in vitro, they inhibited cytokine-induced MMP expression to a lesser extent than parent tetracyclines. This was compensated by an improved inhibition of MMP catalytic activity. Since inhibition of collagen degradation was maintained these derivatives could be potent drug candidates for cartilage-targeted chondroprotective treatment.
authors.affiliation: INSERM 484, Clermont-Ferrand F-63500, France. vidal@inserm484.u-clermont1.fr
authors.forename: Aurélien
authors.initials: A
authors.lastname: Vidal
authors.forename: Massimo
authors.initials: M
authors.lastname: Sabatini
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Rolland-Valognes
authors.forename: Pierre
authors.initials: P
authors.lastname: Renard
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Madelmont
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Mounetou
mesh_terms: D000818:Animals; D002358:Cartilage, Articular / Q000187:drug effects / Q000201:enzymology; D002813:Chondrosarcoma / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D003094:Collagen / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000378:metabolism; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011509:Proteoglycans / Q000187:drug effects / Q000378:metabolism; D011817:Rabbits; D013754:Tetracyclines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D011509:Proteoglycans; D013754:Tetracyclines; D003094:Collagen; D020782:Matrix Metalloproteinases