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Phosphinic Pseudo-Tripeptides as Potent Inhibitors of Matrix Metalloproteinases: A Structure−Activity Study

1999; American Chemical Society; Volume: 42; Issue: 14 Linguagem: Inglês

10.1021/jm9900164

1520-4804

Stamatia Vassiliou, Artur Mucha, Philippe Cuniasse, Dimitris Georgiadis, Karine Lucet-Levannier, Fabrice Beau, Rama Kannan, Gillian Murphy, Vera Knäuper, Marie‐Christine Rio, Paul Basset, Athanasios Yiotakis, Vincent Dive,

Chemical Synthesis and Analysis

Several phosphinic pseudo-tripeptides of general formula R-XaaPsi(PO(2)-CH(2))Xaa'-Yaa'-NH(2) were synthesized and evaluated for their in vitro activities to inhibit stromelysin-3, gelatinases A and B, membrane type-1 matrix metalloproteinase, collagenases 1 and 2, and matrilysin. With the exception of collagenase-1 and matrilysin, phosphinic pseudo-tripeptides behave as highly potent inhibitors of matrix metalloproteinases, provided they contain in P(1)' position an unusual long aryl-alkyl substituent. Study of structure-activity relationships regarding the influence of the R and Xaa' substituents in this series may contribute to the design of inhibitors able to block only a few members of the matrix metalloproteinase family.