2. Academic Validation
  3. Targeting FtsZ for antituberculosis drug discovery: noncytotoxic taxanes as novel antituberculosis agents

Targeting FtsZ for antituberculosis drug discovery: noncytotoxic taxanes as novel antituberculosis agents

  • J Med Chem. 2006 Jan 26;49(2):463-6. doi: 10.1021/jm050920y.
Qing Huang 1,  Fumiko Kirikae,  Teruo Kirikae,  Antonella Pepe,  Amol Amin,  Laurel Respicio,  Richard A Slayden,  Peter J Tonge,  Iwao Ojima
Affiliations

Affiliation

  • 1 Department of Chemistry, State University of New York at Stony Brook, New York 11794-3400, USA.
PMID: 16420032 DOI: 10.1021/jm050920y
Abstract

Screening of 120 taxanes identified a number of compounds that exhibited significant antituberculosis activity. Rational optimization of selected compounds led to the discovery that the C-seco-taxane-multidrug-resistance (MDR) reversal agents (C-seco-TRAs) are noncytotoxic at the upper limit of solubility and detection (>80 microM), while maintaining MIC(99) values of 1.25-2.5 microM against drug-resistant and drug-sensitive strains of Mycobacterium tuberculosis (MTB). Treatment of MTB cells with TRA 3aa and 10a at the MIC caused filamentation and prolongation of the cells, a phenotypic response to FtsZ inactivation.

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