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

Qing Huang; Fumiko Kirikae; Teruo Kirikae; Antonella Pepe; Amol Amin; Laurel Respicio; Richard A. Slayden; Peter J. Tonge; Iwao Ojima

doi:10.1021/jm050920y

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

Qing Huang
, Fumiko Kirikae
, Teruo Kirikae
, Antonella Pepe
, Amol Amin
, Laurel Respicio
, Richard A. Slayden
, Peter J. Tonge
, Iwao Ojima

Chemistry

Stony Brook University
National Center for Global Health and Medicine
Colorado State University

Research output: Contribution to journal › Article › peer-review

103 Scopus citations

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 non-cytotoxic at the upper limit of solubility and detection (>80 μM), while maintaining MIC₉₉ values of 1,25-2.5 μM 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.

Original language	English
Pages (from-to)	463-466
Number of pages	4
Journal	Journal of Medicinal Chemistry
Volume	49
Issue number	2
DOIs	https://doi.org/10.1021/jm050920y
State	Published - Jan 26 2006

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title = "Targeting FtsZ for antituberculosis drug discovery: Noncytotoxic taxanes as novel antituberculosis agents",

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 non-cytotoxic at the upper limit of solubility and detection (>80 μM), while maintaining MIC99 values of 1,25-2.5 μM 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.",

author = "Qing Huang and Fumiko Kirikae and Teruo Kirikae and Antonella Pepe and Amol Amin and Laurel Respicio and Slayden, \{Richard A.\} and Tonge, \{Peter J.\} and Iwao Ojima",

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doi = "10.1021/jm050920y",

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T1 - Targeting FtsZ for antituberculosis drug discovery

T2 - Noncytotoxic taxanes as novel antituberculosis agents

AU - Huang, Qing

AU - Kirikae, Fumiko

AU - Kirikae, Teruo

AU - Pepe, Antonella

AU - Amin, Amol

AU - Respicio, Laurel

AU - Slayden, Richard A.

AU - Tonge, Peter J.

AU - Ojima, Iwao

PY - 2006/1/26

Y1 - 2006/1/26

N2 - 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 non-cytotoxic at the upper limit of solubility and detection (>80 μM), while maintaining MIC99 values of 1,25-2.5 μM 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.

AB - 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 non-cytotoxic at the upper limit of solubility and detection (>80 μM), while maintaining MIC99 values of 1,25-2.5 μM 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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M3 - Article

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EP - 466

JO - Journal of Medicinal Chemistry

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IS - 2

ER -

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

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