title: Inhibition of thymidine phosphorylase (PD-ECGF) from SD-lymphoma by phosphonomethoxyalkyl thymines.
abstract: A series of thymine phosphonomethoxyalkyl derivatives were evaluated for their ability to inhibit thymidine phosphorylase (dThdPase) purified from rat spontaneous T-cell lymphoma. A kinetic study of thymidine phosphorolysis catalyzed by dThdPase was performed with thymidine and/or inorganic phosphate as substrates. Data show that the substantial inhibitory effect of these acyclic nucleotide analogues is decreasing in the order of (R)-FPMPT>(S)-FPMPT>or=(R)-HPMPT>(S)-PMPT>(S)-HPMPT>PMET>or=(R)-PMPT. The inhibitory potency (K(i)/(dThd)K(m)) of the most efficient inhibitors from this series against T-cell lymphoma enzyme is 0.0026 for (R)-FPMPT and 0.0048 for (S)-FPMPT. The studied compounds do not inhibit Escherichia coli and human enzyme and possess lower inhibitory potency against rat liver thymidine phosphorylase.
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, 166 10 Prague, Czech Republic. votruba@uochb.cas.cz <votruba@uochb.cas.cz>
authors.forename: Ivan
authors.initials: I
authors.lastname: Votruba
authors.forename: Karel
authors.initials: K
authors.lastname: Pomeisl
authors.forename: Eva
authors.initials: E
authors.lastname: Tloust'ová
authors.forename: Antonín
authors.initials: A
authors.lastname: Holý
authors.forename: Berta
authors.initials: B
authors.lastname: Otová
mesh_terms: D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D016399:Lymphoma, T-Cell / Q000201:enzymology*; D063065:Organophosphonates / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013939:Thymidine Phosphorylase / Q000037:antagonists & inhibitors*; D013941:Thymine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013946:Thymopoietins / Q000494:pharmacology*
chemical_list: C541639:1-(3-fluoro-2-(phosphonomethoxy)propyl)thymine; D004791:Enzyme Inhibitors; D063065:Organophosphonates; D013946:Thymopoietins; D013939:Thymidine Phosphorylase; D013941:Thymine