title: Design, synthesis and biological evaluation of novel L-isoserine tripeptide derivatives as aminopeptidase N inhibitors.
abstract: Aminopeptidase N (APN/CD13) is one of the essential proteins for tumour invasion, angiogenesis and metastasis as it is over-expressed on the surface of different tumour cells. Based on our previous work that L-isoserine dipeptide derivatives were potent APN inhibitors, we designed and synthesized L-isoserine tripeptide derivatives as APN inhibitors. Among these compounds, one compound 16l (IC₅₀ = 2.51 ± 0.2 µM) showed similar inhibitory effect compared with control compound Bestatin (IC₅₀ = 6.25 ± 0.4 µM) and it could be used as novel lead compound for the APN inhibitors development as anticancer agents in the future.
authors.affiliation: Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, Shandong, China.
authors.forename: Huili
authors.initials: H
authors.lastname: Pan
authors.forename: Kanghui
authors.initials: K
authors.lastname: Yang
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.forename: Yingying
authors.initials: Y
authors.lastname: Xu
authors.forename: Yuqi
authors.initials: Y
authors.lastname: Jiang
authors.forename: Yumei
authors.initials: Y
authors.lastname: Yuan
authors.forename: Xiaopan
authors.initials: X
authors.lastname: Zhang
authors.forename: Wenfang
authors.initials: W
authors.lastname: Xu
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D018826:CD13 Antigens / Q000037:antagonists & inhibitors* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D018922:HL-60 Cells; D006801:Humans; D020014:K562 Cells; D008958:Models, Molecular; D008968:Molecular Conformation; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D012694:Serine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D009842:Oligopeptides; D011480:Protease Inhibitors; D012694:Serine; C072421:isoserine; D018826:CD13 Antigens