A new class of methionine aminopeptidase (MetAP) inhibitors, which contain an internal hydroxamate (N-acyl-N-alkylhydroxylamine) core as the metal-chelating group, has been designed, synthesized, and tested. The compounds exhibited reversible, competitive inhibition against Escherichia coli MetAP as well as human MetAP-1 and MetAP-2. The most potent inhibitor had a Ki value of 2.5 μM and> 20-fold selectivity toward E. coli MAP.
[Balsamo, A.; Belfiore, M. S.; Macchia, M.; Martini, C.; Nencetti, S.; et al. European Journal of Medicinal Chemistry, 1994 , vol. 29, # 10 p. 787 - 794]
