Structural diversity of nucleoside phosphonic acids as a key factor in the discovery of potent inhibitors of rat T-cell lymphoma thymidine phosphorylase |
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Authors: | Petr Kočalka Dominik Rejman Václav Vaněk Markéta Rinnová Ivana Tomečková Šárka Králíková Magdalena Petrová Ondřej Páv Radek Pohl Miloš Buděšínský Radek Liboska Zdeněk Točík Natalya Panova Ivan Votruba Ivan Rosenberg |
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Affiliation: | Institute of Organic Chemistry and Biochemistry, Academy of Sciences v. v. i., Flemingovo 2, 166 10 Prague 6, Czech Republic |
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Abstract: | 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. |
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