Synthesis and anti-angiogenetic activity evaluation of N-(3-aryl acryloyl)aminosaccharide derivatives.
In order to find novel potent inhibitors for signal pathways of FGF/FGFR, nineteen N-(3-aryl acryloyl)aminosaccharide derivatives were designed and synthesized based on the binding sites of FGF and oligosaccharides of heparin. Their structures were confirmed by IR, (1)H NMR, (13)C NMR, MS and elemental analysis. The nineteen target compounds were evaluated for biological activity against HUVEC cell. In vitro assays showed that compound 10s (IC50=5.3μM) exhibited comparable inhibitory effects on endothelial cell growth with topotecan (IC50=2.7μM). Compound 10s (10μg/egg) also showed obvious anti-angiogenetic activity in the in vivo chicken chorio allantoic membrane (CAM) assay, and the potency was similar to topotecan (10μg/egg).
Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China.
Kun
K
Liu
Shuowei
S
Yao
Yinghan
Y
Lou
Yungen
Y
Xu
D000178:Acrylamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D020533:Angiogenesis Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002645:Chickens; D049033:Chorioallantoic Membrane / Q000166:cytology / Q000187:drug effects*; D002934:Cinnamates / Q000737:chemistry; D004187:Disaccharides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects*; D006801:Humans; D015394:Molecular Structure; D013329:Structure-Activity Relationship
D000178:Acrylamides; D020533:Angiogenesis Inhibitors; D002934:Cinnamates; D004187:Disaccharides; C029010:cinnamic acid
Aminosaccharide; Fibroblast growth factor; Heparin mimic; Tumor angiogenesis inhibitors