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ID: ALA1926583

Journal: Bioorg Med Chem

Title: Synthesis and inhibitory activity of thymidine analogues targeting Mycobacterium tuberculosis thymidine monophosphate kinase.

Authors: Van Poecke S, Munier-Lehmann H, Helynck O, Froeyen M, Van Calenbergh S.

Abstract: We report on Mycobacterium tuberculosis thymidine monophosphate kinase (TMPKmt) inhibitory activities of a series of new 3'- and 5'-modified thymidine analogues including α- and β-derivatives. In addition, several analogues were synthesized in which the 4-oxygen was replaced by a more lipophilic sulfur atom to probe the influence of this modification on TMPKmt inhibitory activity. Several compounds showed an inhibitory potency in the low micromolar range, with the 5'-arylthiourea 4-thio-α-thymidine analogue being the most active one (K(i)=0.17 μM). This compound was capable of inhibiting mycobacteria growth at a concentration of 25 μg/mL.

CiteXplore: 22061826

DOI: 10.1016/j.bmc.2011.10.021