Inhibition of endothelial cell proliferation by per-O-acetylated mannose conjugates.
BACKGROUND
The inhibition of angiogenesis, defined as the process of new blood vessel formation, represents a promising strategy for treating cancer.


METHODS
The inhibitory properties of two N-(per-O-acetylated-beta-D- mannopyranosyl)thiophene-2-carboxamides derivatives (AMTCs, [1],[2]), N-(2,3,4,6-tetra-O-ethoxycarbonyl-beta-D-mannopyranosyl)- thiophene-2-carboxamide [3] and of 2,3,4,6-tetra-O-acetyl-beta-D-mannopyranosyl-acetamide [4] on the growth of bovine aortic endothelial cells (BAECs) induced by basic fibroblast growth factor (bFGF) were assessed using a [3H]thymidine incorporation assay. The cellular uptake of AMTCs and the non-acetylated homologue (MTC) into BAEC were compared using mass spectrometry analysis of cell lysates.


RESULTS
AMTCs [1],[2]), at 80 microM, reversed the increase of [3H]thymidine incorporation induced by bFGF, suggesting that these compounds inhibited bFGF-induced proliferative response in BAECs. The acetamide [4] was inactive showing the importance of the thiophene carboxamide for biological activity. The results of a study of AMTC uptake into BAEC suggest that AMTC is rapidly converted to its non-acetylated counterpart.


CONCLUSIONS
The promising results obtained with AMTCs as inhibitors of BAEC growth could lead to the development of novel angiogenesis inhibitors.
Zaric
Violeta
V
UCD School of Biomolecular and Biomedical Science, Conway Institute and University College Dublin, Belfield, Dublin 4, Ireland.
Doyle
Dearbhla
D
Murphy
Paul V
PV
O'Boyle
Kathy M
KM
D000081:Acetamides / Q000493:pharmacokinetics / Q000494:pharmacology; D000107:Acetylation; D000818:Animals; D001011:Aorta / Q000166:cytology; D002417:Cattle; D048708:Cell Growth Processes / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D004261:DNA Replication / Q000187:drug effects; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects*; D016222:Fibroblast Growth Factor 2 / Q000037:antagonists & inhibitors; D008358:Mannose / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology*; D013058:Mass Spectrometry
D000081:Acetamides; D016222:Fibroblast Growth Factor 2; D004247:DNA; D008358:Mannose