Hybrids of 1-deoxynojirimycin and aryl-1,2,3-triazoles and biological studies related to angiogenesis |
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Authors: | Zhao Yunxue Zhou Ying O'Boyle Kathy M Murphy Paul V |
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Institution: | UCD School of Biomolecular and Biomedical Science and the UCD Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland. |
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Abstract: | Hybrids of 1-deoxynojirimycin (DNJ) and aryl-1,2,3-triazole have been synthesized with a view to identifying an inhibitor of both alpha-glucosidase and methionine aminopeptidase 2 (MetAP2). One compound was a potent inhibitor of alpha-glucosidase at both the enzyme and cellular level, and this agent also inhibited bovine aortic endothelial cell (BAEC) growth and tube formation. The anti-proliferative activity of this hybrid is due to its ability to induce cell-cycle arrest in the G(1) phase. The novel agent caused a reduction in the expression of cyclin D1 but did not promote apoptosis or inhibit the phosphorylation of ERK1/2. These observations indicate that its mechanism of action is distinct from fumagillin and its analogues, which inhibit MetAP2. Stress-fibre assembly in BAECs was abolished by the novel agent indicating that the inhibition of BAEC tube formation observed is partially a result of a reduction in cell motility. |
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