Incorporation of Bulky and Cationic Cyclam-Triazole Moieties into Marimastat Can Generate Potent MMP Inhibitory Activity without Inducing Cytotoxicity.

ABSTRACT: The synthesis and matrix metalloproteinase (MMP) inhibitory activity of a cyclam-marimastat conjugate and its metal complexes are described. The conjugate, synthesized with a copper(I)-catalyzed Huisgen 1,3-dipolar cycloaddition ("click" reaction), contains two zinc-binding groups (ZBGs). The metal complexation behavior with copper(II) and zinc(II) was investigated using UV/Vis spectrophotometry and (1)H NMR spectroscopy, respectively, demonstrating that the first equivalent of the metal ion was chelated by the cyclam-triazole moiety rather than the hydroxamic acid site. Thus, the corresponding mononuclear metal-cyclam complexes were successfully prepared with one equivalent of the metal salt. Both the cyclam-marimastat conjugate and its metal complexes exhibited slightly reduced potency a

SUBMITTER: Yu M 

PROVIDER: S-EPMC3703814 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature