title: Design, synthesis and preliminary activity evaluation of novel 3-amino-2-hydroxyl-3-phenylpropanoic acid derivatives as aminopeptidase N/CD13 inhibitors.
abstract: Aminopeptidase N (APN/CD13) over expressed on tumour cells, plays a critical role in tumour invasion, metastasis and tumour angiogenesis. In this article, we described the design, synthesis and preliminary activity studies of novel 3-amino-2-hydroxyl-3-phenylpropanoic acid derivatives as APN inhibitors. The in vitro enzymatic inhibitions on APN from porcine kidney showed that compound 7e had the most potent inhibitory activity against APN with the IC(50) value to 1.26 ± 0.01 μM, which is better than that of bestatin (IC(50) = 2.55 ± 0.11 μM). In addition, compound 7e also showed better inhibitory activity against APN on human ovary clear cell carcinoma cell ES-2 than bestatin with the IC(50) value to 30.19 ± 1.02 μM versus 60.61 ± 0.1 μM. Compound 7e could be used as the lead compound in the future for anti-cancer agent research.
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Shan Dong University, Ji'nan, China.
authors.forename: Xiaopan
authors.initials: X
authors.lastname: Zhang
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.forename: Jinhong
authors.initials: J
authors.lastname: Feng
authors.forename: Yumei
authors.initials: Y
authors.lastname: Yuan
authors.forename: Hao
authors.initials: H
authors.lastname: Fang
authors.forename: Wenfang
authors.initials: W
authors.lastname: Xu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D018826:CD13 Antigens / Q000037:antagonists & inhibitors*; D045744:Cell Line, Tumor; D060326:Chemistry Techniques, Synthetic; D015195:Drug Design; D005260:Female; D020128:Inhibitory Concentration 50; D007668:Kidney / Q000201:enzymology; D007930:Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D062105:Molecular Docking Simulation; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000473:pathology; D010666:Phenylpropionates / Q000737:chemistry*; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D010666:Phenylpropionates; D011480:Protease Inhibitors; C035253:3-phenylpropionic acid; D018826:CD13 Antigens; D007930:Leucine; C012211:ubenimex