title: Syntheses of 1-[2-(Phosphonomethoxy)Alkyl] thymine monophosphates and an evaluation of their inhibitory activity toward human thymidine phosphorylase.
abstract: A series of new monophosphates of 1-[2-(phosphonomethoxy)alkyl]thymines, such as PMPTp(,) 3-MeO-PMPTp, HPMPTp, and FPMPTp, were synthesized and tested for their ability to inhibit human thymidine phosphorylase. Kinetic measurements of enzyme activity were performed using thymidine and inorganic phosphate as the substrates. The data show that some monophosphates provide a considerable increase of the multisubstrate inhibitory effect. The highest inhibitory potency was found with (R)-FPMPTp 4c (K (i) (dT) = 4.09 ± 0.47 μM, K (i)(P(i)) = 2.13 ± 0.29 μM) and (R) 3-MeO-PMPTp 4d (K (i) (dT) = 5.78 ± 0.71 μM, K (i)(P(i)) = 2.71 ± 0.37 μM).
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, v.v.i. , Prague, Czech Republic. pomeisl@uochb.cas.cz
authors.forename: Karel
authors.initials: K
authors.lastname: Pomeisl
authors.forename: Květoslava
authors.initials: K
authors.lastname: Horská
authors.forename: Radek
authors.initials: R
authors.lastname: Pohl
authors.forename: Jiří
authors.initials: J
authors.lastname: Blažek
authors.forename: Marcela
authors.initials: M
authors.lastname: Krečmerová
mesh_terms: D000818:Animals; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D007700:Kinetics; D015394:Molecular Structure; D063065:Organophosphonates / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D010710:Phosphates; D010766:Phosphorylation; D013936:Thymidine; D013939:Thymidine Phosphorylase / Q000037:antagonists & inhibitors*; D013941:Thymine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology
chemical_list: C541639:1-(3-fluoro-2-(phosphonomethoxy)propyl)thymine; D063065:Organophosphonates; D010710:Phosphates; D013939:Thymidine Phosphorylase; D013941:Thymine; D013936:Thymidine