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.
Publication types
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Comparative Study
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Actin Cytoskeleton / drug effects
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Actin Cytoskeleton / ultrastructure
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Antineoplastic Agents / pharmacology
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Antitubercular Agents / chemical synthesis*
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Antitubercular Agents / chemistry
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Antitubercular Agents / pharmacology
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Bacterial Proteins / antagonists & inhibitors*
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Bacterial Proteins / chemistry
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Biopolymers
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Cytoskeletal Proteins / antagonists & inhibitors*
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Cytoskeletal Proteins / chemistry
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Drug Resistance, Multiple, Bacterial / drug effects
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Microbial Sensitivity Tests
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Mycobacterium tuberculosis / drug effects
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Mycobacterium tuberculosis / ultrastructure
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Paclitaxel / pharmacology
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Structure-Activity Relationship
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Taxoids / chemical synthesis*
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Taxoids / chemistry
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Taxoids / pharmacology
Substances
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Antineoplastic Agents
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Antitubercular Agents
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Bacterial Proteins
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Biopolymers
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Cytoskeletal Proteins
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FtsZ protein, Bacteria
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Taxoids
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Paclitaxel