Thymidine and thymidine-5'-O-monophosphate analogues as inhibitors of Mycobacterium tuberculosis thymidylate kinase

Veerle Vanheusden; Philippe Van Rompaey; Hélène Munier-Lehmann; Sylvie Pochet; Piet Herdewijn; Serge Van Calenbergh

doi:10.1016/s0960-894x(03)00643-7

Thymidine and thymidine-5'-O-monophosphate analogues as inhibitors of Mycobacterium tuberculosis thymidylate kinase

Bioorg Med Chem Lett. 2003 Sep 15;13(18):3045-8. doi: 10.1016/s0960-894x(03)00643-7.

Authors

Veerle Vanheusden¹, Philippe Van Rompaey, Hélène Munier-Lehmann, Sylvie Pochet, Piet Herdewijn, Serge Van Calenbergh

Affiliation

¹ Laboratory for Medicinal Chemistry (FFW), Ghent University, Harelbekestraat 72, B-9000 Gent, Belgium.

PMID: 12941330
DOI: 10.1016/s0960-894x(03)00643-7

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antitubercular Agents / chemical synthesis*
Antitubercular Agents / pharmacology
Enzyme Inhibitors / chemical synthesis
Enzyme Inhibitors / pharmacology
Inhibitory Concentration 50
Kinetics
Mycobacterium tuberculosis / enzymology*
Nucleoside-Phosphate Kinase / antagonists & inhibitors*
Structure-Activity Relationship
Thymidine / analogs & derivatives*
Thymidine / chemical synthesis
Thymidine / pharmacology
Thymine Nucleotides / chemical synthesis*
Thymine Nucleotides / pharmacology

Substances

Antitubercular Agents
Enzyme Inhibitors
Thymine Nucleotides
Nucleoside-Phosphate Kinase
dTMP kinase
Thymidine