Incorporation of bulky and cationic cyclam-triazole moieties into marimastat can generate potent MMP inhibitory activity without inducing cytotoxicity

Abstract

Choices, choices: A conjugate of cyclam and the matrix metalloproteinase (MMP) inhibitor marimastat was synthesized to give a compound with two potential zinc-binding groups (ZBGs). The first equivalent of Cu(II) or Zn(II) was chelated by the cyclam-triazole moiety rather than the hydroxamic acid. Both the conjugate and its metal complexes exhibited potent and selective MMP inhibitory activity, and displayed no cytotoxicity, suggesting future applications in the imaging of MMP activity. © 2013 The Authors.