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

Veerle Vanheusden (1) , Philippe van Rompaey (1) , Hélène Munier-Lehmann (2) , Sylvie Pochet (3) , Piet Herdewijn (4) , Serge van Calenbergh (1)

1 UGENT - Universiteit Gent = Ghent University
2 CSM - Chimie Structurale des Macromolécules
3 Chimie Organique
4 KU Leuven - Catholic University of Leuven - Katholieke Universiteit Leuven

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.

Domains: Life Sciences [q-bio]

Veerle Vanheusden, Philippe van Rompaey, Hélène Munier-Lehmann, Sylvie Pochet, Piet Herdewijn, et al.. Thymidine and thymidine-5'-O-monophosphate analogues as inhibitors of Mycobacterium tuberculosis thymidylate kinase.. Bioorganic and Medicinal Chemistry Letters, 2003, 13 (18), pp.3045-8. ⟨10.1016/S0960-894X(03)00643-7⟩. ⟨pasteur-00166206⟩