title: Thymidine and thymidine-5'-O-monophosphate analogues as inhibitors of Mycobacterium tuberculosis thymidylate kinase.
abstract: The affinity of a series of 2', 3'- and 5-modified thymidine analogues for Mycobacterium tuberculosis thymidine monophosphate kinase (TMPKmt) was evaluated. The affinities of several non-phosphorylated analogues are in the same order of magnitude as those of their phosphorylated congeners. In view of drug delivery problems associated with phosphorylated compounds, these 'free' nucleosides seem more promising leads in the search of TMPKmt inhibitors as novel anti-tuberculosis agents.
authors.affiliation: Laboratory for Medicinal Chemistry (FFW), Ghent University, Harelbekestraat 72, B-9000 Gent, Belgium.
authors.forename: Veerle
authors.initials: V
authors.lastname: Vanheusden
authors.forename: Philippe
authors.initials: P
authors.lastname: Van Rompaey
authors.forename: Hélène
authors.initials: H
authors.lastname: Munier-Lehmann
authors.forename: Sylvie
authors.initials: S
authors.lastname: Pochet
authors.forename: Piet
authors.initials: P
authors.lastname: Herdewijn
authors.forename: Serge
authors.initials: S
authors.lastname: Van Calenbergh
mesh_terms: D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D007700:Kinetics; D009169:Mycobacterium tuberculosis / Q000201:enzymology*; D009703:Nucleoside-Phosphate Kinase / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D013936:Thymidine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D013942:Thymine Nucleotides / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D000995:Antitubercular Agents; D004791:Enzyme Inhibitors; D013942:Thymine Nucleotides; D009703:Nucleoside-Phosphate Kinase; C020093:dTMP kinase; D013936:Thymidine