Searching for new cures for tuberculosis: Design, synthesis, and biological evaluation of 2-methylbenzothiazoles

Qingqing Huang, Jialin Mao, Baojie Wan, Yuehong Wang, Reto Brun, Scott G. Franzblau, Alan P. Kozikowski

Research output: Contribution to journalArticle

Abstract

The actual development and clinical use of new therapeutics for tuberculosis (TB) have remained stagnant for years because of the complexity of the disease process, the treatment of which at present requires the administration of drug combinations over a 6month period. There is thus an urgent need for the discovery and development of novel, more active, and less toxic anti-TB agents. In this study, we report on the chemistry and biology of a series of potent 5-(2-methylbenzothiazol-5-yloxymethyl) isoxazole-3-carboxamide derivatives, which proved to be active against replicating Mycobacterium tuberculosis (Mtb) H37Rv. The most potent compounds 7j and 7s were found to inhibit Mtb growth at micromolar concentrations, with MICvalues of 1.4 and 1.9 μM, respectively. Impressively, all active compounds were nontoxic toward Vero cells (IC50 > 128 μM). Moreover, the best of these compounds were also tested against protozoan parasites, and some of these compounds were found to show activity, especially against Plasmodium falciparum. These studies thus suggest that certain 2-methylbenzothiazole based compounds may serve as promising lead scaffolds for further elaboration as anti-TB drugs and as possible antimalaria drugs.

Original languageEnglish (US)
Pages (from-to)6757-6767
Number of pages11
JournalJournal of medicinal chemistry
Volume52
Issue number21
DOIs
StatePublished - Nov 12 2009

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ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Cite this

Huang, Q., Mao, J., Wan, B., Wang, Y., Brun, R., Franzblau, S. G., & Kozikowski, A. P. (2009). Searching for new cures for tuberculosis: Design, synthesis, and biological evaluation of 2-methylbenzothiazoles. Journal of medicinal chemistry, 52(21), 6757-6767. https://doi.org/10.1021/jm901112f