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. Materials and 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)-thiophene2-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 [H-3]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 mu M, reversed the increase of [H-3]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 nonacetylated counterpart. Conclusion: The promising results obtained with AMTCs as inhibitors of BAEC growth could lead to the development of novel angiogenesis inhibitors.