| PMID : |
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 (22061826) |
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| titre : |
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Synthesis and inhibitory activity of thymidine analogues targeting Mycobacterium tuberculosis thymidine monophosphate kinase. |
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| auteur(s) : |
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Sara Van Poecke1, Hélène Munier-Lehmann2, Olivier Helynck2, Matheus Froeyen3, Serge Van Calenbergh1 |
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| laboratoire : |
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| résumé : |
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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)=0.17μM). This compound was capable of inhibiting mycobacteria growth at a concentration of 25μg/mL. |
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| domaine : |
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Sciences du Vivant/Biochimie, Biologie Moléculaire
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langue du texte
intégral : |
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Anglais |
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| ISSN : |
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1464-3391 |
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| type de publication : |
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Articles dans des revues avec comité de lecture |
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| DOI : |
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10.1016/j.bmc.2011.10.021 |
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| journal : |
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Bioorg Med Chem |
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| Audience : |
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internationale |
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| date de publication : |
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18/10/2011 |
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date de publication
électronique : |
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18/10/2011 |
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| volume : |
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19 |
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| page, identifiant, ... : |
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epub ahead of print |
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