A new class of antituberculosis agents

P. B. Jones, N. M. Parrish, T. A. Houston, A. Stapon, N. P. Bansal, J. D. Dick, C. A. Townsend

Research output: Contribution to journalArticle

Abstract

Long-chain lipid envelopes are characteristic of mycobacteria such as those that cause tuberculosis and leprosy. Inhibition of fatty acid synthesis or elongation is a strategy demonstrated to be clinically effective against M. tuberculosis. A new class of compounds designed to inhibit the β-ketoacyl synthase reaction of fatty acid synthesis has been developed. Of >30 compounds described, the most active were acetamides containing alkylsulfonyl substituents. Inhibitory activities were acutely sensitive to net charge, chain length, and degree of unsaturation. The most active compound 5 (alkyl = C10) contained a single methylene spacer between the sulfone and carboxamide and exhibited an MIC of 0.75-1.5 μg/mL, comparable to first-line antituberculosis drugs. These compounds are species-specific, exhibiting no significant activity against bacterial species other than M. tuberculosis and closely related strains. The synthesis, biological activity, and specificity of these compounds are described.

Original languageEnglish (US)
Pages (from-to)3304-3314
Number of pages11
JournalJournal of medicinal chemistry
Volume43
Issue number17
DOIs
StatePublished - Aug 24 2000

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ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Cite this

Jones, P. B., Parrish, N. M., Houston, T. A., Stapon, A., Bansal, N. P., Dick, J. D., & Townsend, C. A. (2000). A new class of antituberculosis agents. Journal of medicinal chemistry, 43(17), 3304-3314. https://doi.org/10.1021/jm000149l