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

0345860 - ÚOCHB 2011 RIV GB eng J - Článek v odborném periodiku
Kočalka, Petr - Rejman, Dominik - Vaněk, Václav - Rinnová, Markéta - Tomečková, Ivana - Králíková, Šárka - Petrová, Magdalena - Páv, Ondřej - Pohl, Radek - Buděšínský, Miloš - Liboska, Radek - Točík, Zdeněk - Panova, Natalya - Votruba, Ivan - Rosenberg, Ivan
Structural diversity of nucleoside phosphonic acids as a key factor in the discovery of potent inhibitors of rat T-cell lymphoma thymidine phosphorylase.
Bioorganic and Medicinal Chemistry Letters. Roč. 20, č. 3 (2010), s. 862-865. ISSN 0960-894X. E-ISSN 1464-3405
Grant CEP: GA ČR GA203/09/0820; GA ČR GA202/09/0193; GA MŠMT(CZ) LC06061; GA MŠMT(CZ) LC06077; GA MŠMT 2B06065; GA AV ČR KAN200520801; GA AV ČR 1QS400550501; GA MZd NR9138
Výzkumný záměr: CEZ:AV0Z40550506
Klíčová slova: phosphonate nucleotides * pyrrolidine * thymidine phosphorylase
Kód oboru RIV: CC - Organická chemie
Impakt faktor: 2.661, rok: 2010

Structurally diverse, sugar-modified, thymine-containing nucleoside phosphonic acids were evaluated for their ability to inhibit thymidine phosphorylase 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 .mu.M were selected. Out of them, four compounds strongly inhibited the enzyme with IC50 values in a range of 11–45 nM. These most potent compounds might be bi-substrate analogues.
Trvalý link: http://hdl.handle.net/11104/0187044