Novel potent 2,5-pyrrolidinedione peptidomimetics as aminopeptidase N inhibitors. Design, synthesis and activity evaluation.
A series of novel aminopeptidase N inhibitors with 2,5-pyrrolidinedione scaffold were chemically synthesized. Their preliminary biological activities in enzyme kinetics and cell assay in vitro and anti-metastasis profile in vivo were also evaluated. The results indicated that all the compounds displayed potent inhibitory activity against aminopeptidase N. Compound 8f inhibited aminopeptidase N activity with IC(50) value of 1.0μM and displayed better activity profile in vivo than that of bestatin.
Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Central South University, 172 Tongzipo Road, 410013 Changsha, Hu'nan, China. qbli@csu.edu.cn
Qianbin
Q
Li
Hao
H
Fang
Xuejian
X
Wang
Gaoyun
G
Hu
Qiang
Q
Wang
Wenfang
W
Xu
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; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D057786:Peptidomimetics / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013388:Succinimides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
C574447:2-amino-N-(1-(2-(hydroxyamino)-2-oxoethyl)-2,5-dioxopyrrolidin-3-yl)-3-phenylpropanamide; D000970:Antineoplastic Agents; D057786:Peptidomimetics; D011480:Protease Inhibitors; D013388:Succinimides; D010649:Phenylalanine; D018826:CD13 Antigens