Thymidine and thymidine-5'-O-monophosphate analogues as inhibitors of Mycobacterium tuberculosis thymidylate kinase.
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.
Vanheusden
Veerle
V
Laboratory for Medicinal Chemistry (FFW), Ghent University, Harelbekestraat 72, B-9000 Gent, Belgium.
Van Rompaey
Philippe
P
Munier-Lehmann
Hélène
H
Pochet
Sylvie
S
Herdewijn
Piet
P
Van Calenbergh
Serge
S
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
D000995:Antitubercular Agents; D004791:Enzyme Inhibitors; D013942:Thymine Nucleotides; D009703:Nucleoside-Phosphate Kinase; C020093:dTMP kinase; D013936:Thymidine