title: Novel cyclic-imide peptidomimetics as aminopeptidase N inhibitors. Design, chemistry and activity evaluation. Part I.
abstract: A series of aminopeptidase inhibitors with cyclic-imide scaffold are described. The biological characterization for the piperidinedione analogues revealed that most compounds displayed high inhibitory activity against APN. Among which 4l and 6 showed potent inhibition against APN with the IC(50) value of 5.2 microM and 3.1 microM, respectively. In addition, 6 also displayed good activity in HL-60 cell assay and in vivo anti-metastasis assay. This interesting activity profile may also guide the design of new, specific inhibitors of target mammalian aminopeptidases with 'one-zinc' active site.
authors.affiliation: Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, 44 West Wenhua Road, 250012 Ji'nan, Shandong, PR China.
authors.forename: Qianbin
authors.initials: Q
authors.lastname: Li
authors.forename: Hao
authors.initials: H
authors.lastname: Fang
authors.forename: Xuejian
authors.initials: X
authors.lastname: Wang
authors.forename: Liping
authors.initials: L
authors.lastname: Hu
authors.forename: Wenfang
authors.initials: W
authors.lastname: Xu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D018826:CD13 Antigens / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D020134:Catalytic Domain; D002470:Cell Survival / Q000187:drug effects*; D015195:Drug Design; D004789:Enzyme Activation / Q000187:drug effects*; D018922:HL-60 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D011480:Protease Inhibitors / Q000737:chemistry / Q000494:pharmacology; D011485:Protein Binding
chemical_list: D000970:Antineoplastic Agents; D011480:Protease Inhibitors; D018826:CD13 Antigens