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Journal of Antimicrobial Chemotherapy (2002) 50, 111-114
© 2002 The British Society for Antimicrobial Chemotherapy

2-Alkoxycarbonylaminopyridines: inhibitors of Mycobacterium tuberculosis FtsZ

E. Lucile White*, William J. Suling, Larry J. Ross, Lainne E. Seitz and Robert C. Reynolds

Drug Discovery Division, Southern Research Institute, 2000 Ninth Avenue South, Birmingham, AL 35205, USA

Received 1 October 2001; returned 3 January 2002; revised 1 March 2002; accepted 2 April 2002

Compounds originally designed as putative tubulin inhibitors were tested as antitubercular agents for inhibition of the Mycobacterium tuberculosis analogue of tubulin, FtsZ. Initial screening of 200 2-alkoxycarbonylpyridines found several that inhibited M. tuberculosis growth. Two compounds, SRI-3072 and SRI-7614, inhibited FtsZ polymerization and were equipotent against susceptible and single-drug-resistant strains of M. tuberculosis. In addition, SRI-3072 reduced the growth of M. tuberculosis in mouse bone marrow macrophages. Our results suggest that these types of compound might be developed into antitubercular drugs effective against the current multidrug-resistant strains of M. tuberculosis.

* Corresponding author. Tel: +1-205-581-2344; Fax: +1-205-581-2877; E-mail: white{at}sri.org


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