title: Structural diversity of nucleoside phosphonic acids as a key factor in the discovery of potent inhibitors of rat T-cell lymphoma thymidine phosphorylase.
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 IC(50) values below 1 microM were selected. Out of them, four compounds strongly inhibited the enzyme with IC(50) values lying in a range of 11-45 nM. These most potent compounds might be bi-substrate analogues.
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences vvi, Flemingovo 2, 166 10 Prague 6, Czech Republic.
authors.forename: Petr
authors.initials: P
authors.lastname: Kocalka
authors.forename: Dominik
authors.initials: D
authors.lastname: Rejman
authors.forename: Václav
authors.initials: V
authors.lastname: Vanek
authors.forename: Markéta
authors.initials: M
authors.lastname: Rinnová
authors.forename: Ivana
authors.initials: I
authors.lastname: Tomecková
authors.forename: Sárka
authors.initials: S
authors.lastname: Králíková
authors.forename: Magdalena
authors.initials: M
authors.lastname: Petrová
authors.forename: Ondrej
authors.initials: O
authors.lastname: Páv
authors.forename: Radek
authors.initials: R
authors.lastname: Pohl
authors.forename: Milos
authors.initials: M
authors.lastname: Budesínský
authors.forename: Radek
authors.initials: R
authors.lastname: Liboska
authors.forename: Zdenek
authors.initials: Z
authors.lastname: Tocík
authors.forename: Natalya
authors.initials: N
authors.lastname: Panova
authors.forename: Ivan
authors.initials: I
authors.lastname: Votruba
authors.forename: Ivan
authors.initials: I
authors.lastname: Rosenberg
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D006801:Humans; D020128:Inhibitory Concentration 50; D016399:Lymphoma, T-Cell / Q000201:enzymology*; D009705:Nucleosides / Q000737:chemistry* / Q000494:pharmacology; D063065:Organophosphonates / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D013939:Thymidine Phosphorylase / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D009705:Nucleosides; D063065:Organophosphonates; D013939:Thymidine Phosphorylase