title: Novel β-dicarbonyl derivatives as inhibitors of aminopeptidase N (APN).
abstract: Most zinc metalloproteases are over-expressed in tumor cells and play a critical role in the genesis, development, and metastasis of tumors. Novel zinc binding groups (ZBGs) represent a novel strategy to obtain optimal potency and selectivity for zinc metalloproteases inhibitors. Here we described the design, synthesis, and biological studies of novel β-dicarbonyl derivatives as aminopeptidase N (APN/CD13) inhibitors. The results demonstrated that some compounds exhibited moderate to good inhibitory activities against APN with compound 5c being the most potent, suggesting that 5c could serve as new lead for the future APN inhibitor development. The results further confirm our design rationale of β-dicarbonyl moiety as a new ZBG, which may provide a new direction for the design and discovery of zinc metalloproteases inhibitors as new anti-tumor agents.
authors.affiliation: Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, Jinan 250012, PR China.
authors.forename: Chunhua
authors.initials: C
authors.lastname: Ma
authors.forename: Xiaoguang
authors.initials: X
authors.lastname: Li
authors.forename: Xuewu
authors.initials: X
authors.lastname: Liang
authors.forename: Kang
authors.initials: K
authors.lastname: Jin
authors.forename: Jiangying
authors.initials: J
authors.lastname: Cao
authors.forename: Wenfang
authors.initials: W
authors.lastname: Xu
mesh_terms: D018826:CD13 Antigens / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D062105:Molecular Docking Simulation; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology; D011480:Protease Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D015032:Zinc / Q000378:metabolism
chemical_list: D011480:Protease Inhibitors; D018826:CD13 Antigens; D015032:Zinc
keywords: Aminopeptidase N; Anti-tumor; Inhibitor; Zinc binding group; β-Dicarbonyl