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

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

doi:10.1016/s0960-894x(02)00551-6

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

Bioorg Med Chem Lett. 2002 Oct 7;12(19):2695-8. doi: 10.1016/s0960-894x(02)00551-6.

Authors

Veerle Vanheusden¹, 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: 12217356
DOI: 10.1016/s0960-894x(02)00551-6

Abstract

A number of 2'- and 3'-modified thymidine 5'-O-monophosphate analogues were synthesized as potential leads for new anti-mycobacterial drugs. Evaluation of their affinity for Mycobacterium tuberculosis thymidine monophosphate kinase showed that a 2'-halogeno substituent and a 3'-azido function are the most favorable leads for further development of potent inhibitors of this enzyme.

Publication types

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

MeSH terms

Antitubercular Agents / chemical synthesis*
Antitubercular Agents / pharmacology*
Crystallography, X-Ray
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / pharmacology*
Kinetics
Models, Molecular
Mycobacterium tuberculosis / drug effects
Mycobacterium tuberculosis / enzymology*
Nucleoside-Phosphate Kinase / antagonists & inhibitors*
Thymidine Monophosphate / analogs & derivatives*
Thymidine Monophosphate / chemical synthesis*
Thymidine Monophosphate / chemistry

Substances

Antitubercular Agents
Enzyme Inhibitors
Thymidine Monophosphate
Nucleoside-Phosphate Kinase
dTMP kinase