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Original Articles

An investigation of the kinetic and anti-angiogenic properties of plant glycoside inhibitors of thymidine phosphorylase

, , , , , , & show all
Pages 159-167 | Received 09 Jul 2008, Accepted 24 Oct 2008, Published online: 14 Feb 2009
 

Abstract

We investigated the potential of symplocomoside (1) and symponoside (2), glycosides isolated from the bark of Symplocos racemosa to inhibit thymidine phosphorylase (TP) activity and associated angiogenesis. Compound 1 was a reversible, noncompetitive inhibitor of deoxythymidine binding to TP (IC50 = 65.45 ± 5.08 μM; K i = 62.83 ± 2.10 μM) and 2 was a reversible, uncompetitive inhibitor (IC50 = 94.17 ± 4.05 μM; K i = 101.95 ± 1.65 μM). Molecular modeling analysis indicated that both compounds bound at the active site of the enzyme but not solely to amino acid residues involved in catalysis. Both compounds were active in in vitro angiogenic assays inhibiting endothelial cell migration and invasion in Matrigel, but did not inhibit growth factor-induced proliferation and were not cytotoxic. Compound 1 may have potential as an anti-angiogenic and anti-tumor agent.

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