Synthesis of N-heteroaroyl aminosaccharide derivatives as fibroblast growth factor 2 signaling modulators.
Fibroblast growth factor 2 (FGF2) signaling plays an important role in angiogenesis. Heparin/heparan sulfate (HS) is required for FGF2 signaling but heparin mimics either promotes or inhibits FGF2 signaling. To take advantage such properties of heparin mimics, a series of N-heteroaroyl aminosaccharide derivatives were designed and synthesized as FGF2 signaling modulators. The bioactivity was determined in a FGF2 and heparin-dependent cell proliferation assay using FGFR1c expressing BaF3 cells. We found that most of the compounds inhibited heparin- and FGF2-dependent BaF3 cell proliferation while three compounds promoted the cell proliferation. These results suggest that the small molecular heparin mimics approach might be useful in developing novel anti-angiogenic agents.
Dong
Jin
J
Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China.
Yao
Shuowei
S
Zhou
Xiaodong
X
Zhang
Lijuan
L
Xu
Yungen
Y
D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D015870:Gene Expression; D006027:Glycosides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006493:Heparin / Q000378:metabolism; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics / Q000378:metabolism
D006027:Glycosides; D016222:Fibroblast Growth Factor 2; D006493:Heparin; D051496:Receptor, Fibroblast Growth Factor, Type 1