Structural diversity of nucleoside phosphonic acids as a key factor in the discovery of potent inhibitors of rat T-cell lymphoma thymidine phosphorylase

Structurally diverse, sugar-modified, thymine-containing nucleoside phosphonic acids were evaluated for their ability to inhibit thymidine phosphorylase (TP, EC 2.4.2.4) purified from spontaneous T-cell lymphomas of an inbred Sprague-Dawley rat strain. From a large set of tested compounds, among them a number of pyrrolidine-based derivatives, 10 nucleotide analogues with IC50 values below 1 μM were selected. Out of them, four compounds strongly inhibited the enzyme with IC50 values lying in a range of 11–45 nM. These most potent compounds might be bi-substrate analogues.

Potent inhibitors of the rat T-cell lymphoma thymidine phosphorylase with IC50 values within 11–45 nM.Figure optionsDownload as PowerPoint slide