title: Discovery of novel taspine derivatives as antiangiogenic agents.
abstract: VEGFR-2 plays a critical role in vasculogenesis and inhibitors of VEGFR-2 could be used in the treatment of cancer. Taspine was one of the active ingredients screened by using an endothelial cell membrane chromatography and showed inhibition against VEGFR-2. In our research, we explored how the lactone ring and biphenyl scaffold in taspine influence its potent in vitro anticancer and antiangiogenesis activities. Accordingly, we report the design, synthesis, and preliminary evaluation of four novel taspine derivatives as VEGFR-2 inhibitors. The preliminary biological test showed that one of the compounds showed much better inhibitory activities against CACO-2 (IC(50)=52.5nM) and ECV304 (IC(50)=2.67nM) than taspine. This result enlarges the interest in ring-opened taspine derivative skeleton in the search of new antiangiogenesis agents.
authors.affiliation: School of Medicine, Xi'an Jiaotong University, No. 76, Yanta Weststreet, Xi'an, Shaanxi Province 710061, PR China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.forename: Yanmin
authors.initials: Y
authors.lastname: Zhang
authors.forename: Sanqi
authors.initials: S
authors.lastname: Zhang
authors.forename: Sicen
authors.initials: S
authors.lastname: Wang
authors.forename: Langchong
authors.initials: L
authors.lastname: He
mesh_terms: D000470:Alkaloids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D020533:Angiogenesis Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001665:Binding Sites; D001713:Biphenyl Compounds / Q000737:chemistry; D020134:Catalytic Domain; D045744:Cell Line, Tumor; D003198:Computer Simulation; D055808:Drug Discovery; D006801:Humans; D006860:Hydrogen Bonding; D007783:Lactones / Q000737:chemistry; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000470:Alkaloids; D020533:Angiogenesis Inhibitors; D001713:Biphenyl Compounds; D007783:Lactones; D047428:Protein Kinase Inhibitors; D040301:Vascular Endothelial Growth Factor Receptor-2; C010574:biphenyl; C018394:taspine