title: Design, synthesis, and activity evaluation of a new 5-fluorouracil prodrug containing an Asn-Gly-Arg(NO2)COOCH3 tripeptide.
abstract: Aminopeptidase N (APN/CD13) of the M1 family is a broad specificity enzyme that is intimately involved in tumor angiogenesis and metastasis. Asparagine-glycine-arginine (NGR) is a tumor-homing tripeptide, which can selectively combine with APN/CD13 that is overexpressed on the surface of some tumor cells. Various anti-tumor drugs can be conjugated to NGR to improve selectivity, efficacy, and to decrease drug toxicity. In this study, a tripeptide NGR(NO2) was synthesized and conjugated with 5-fluorouracil. The anti-tumor activities of this new prodrug were evaluated in vivo. More significant anti-tumor effects were observed over the parent 5-fluorouracil.
authors.affiliation: Institute of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, 44 West Wenhua Road, Jinan, Shandong, 250012, China.
authors.forename: Yepeng
authors.initials: Y
authors.lastname: Luan
authors.forename: Fanbo
authors.initials: F
authors.lastname: Jing
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.forename: Mingming
authors.initials: M
authors.lastname: Zou
authors.forename: Xuejian
authors.initials: X
authors.lastname: Wang
authors.forename: Yuping
authors.initials: Y
authors.lastname: Jia
authors.forename: Ning
authors.initials: N
authors.lastname: Liu
authors.forename: Jiajia
authors.initials: J
authors.lastname: Mou
authors.forename: Wenfang
authors.initials: W
authors.lastname: Xu
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D018826:CD13 Antigens / Q000737:chemistry / Q000378:metabolism*; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D004338:Drug Combinations; D015195:Drug Design; D005260:Female; D005472:Fluorouracil / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects; D006801:Humans; D007797:Laminin / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D011355:Prodrugs / Q000737:chemistry* / Q000494:pharmacology; D011509:Proteoglycans / Q000378:metabolism; D012510:Sarcoma 180 / Q000188:drug therapy* / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
chemical_list: C000594742:13F-1 compound; D000964:Antimetabolites, Antineoplastic; D004338:Drug Combinations; D007797:Laminin; C526428:NGR peptide; D009842:Oligopeptides; D011355:Prodrugs; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen; D018826:CD13 Antigens; D005472:Fluorouracil