title: Novel indoline-2,3-dione derivatives as inhibitors of aminopeptidase N (APN).
abstract: Aminopeptidase N (APN/CD13), as a zinc-containing ectoenzyme, plays a critical role in the process of tumor angiogenesis, invasion and metastasis. Through the docking-based virtual screening of chemical databases and the further activity assay, we discovered that compound 10c exhibits potent and selective inhibitory ability towards APN. In addition, a series of indoline-2,3-dione derivates have been designed and synthesized as APN inhibitors. The results of preliminary activity evaluation showed that compound 12a (IC(50) = 0.074 ± 0.0026 μM) exhibited the best inhibitory activity against APN, which could be used for further anticancer agent research.
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Shandong University, 44, West Culture Road, Jinan, Shandong 250012, China.
authors.forename: Kang
authors.initials: K
authors.lastname: Jin
authors.forename: Xiaopan
authors.initials: X
authors.lastname: Zhang
authors.forename: Chunhua
authors.initials: C
authors.lastname: Ma
authors.forename: Yingying
authors.initials: Y
authors.lastname: Xu
authors.forename: Yumei
authors.initials: Y
authors.lastname: Yuan
authors.forename: Wenfang
authors.initials: W
authors.lastname: Xu
mesh_terms: D018826:CD13 Antigens / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D015394:Molecular Structure; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D007211:Indoles; D011480:Protease Inhibitors; C572590:indoline-2,3-dione; D018826:CD13 Antigens