The 7-phenyl benzoxaborole series is active against Mycobacterium tuberculosis

Aaron Korkegian; Theresa O'Malley; Yi Xia; Yasheen Zhou; David S. Carter; Bjorn Sunde; Lindsay Flint; Dean Thompson; Thomas R. Ioerger; Jim Sacchettini; M. R.K. Alley; Tanya Parish

doi:10.1016/j.tube.2017.11.003

The 7-phenyl benzoxaborole series is active against Mycobacterium tuberculosis

Aaron Korkegian
, Theresa O'Malley
, Yi Xia
, Yasheen Zhou
, David S. Carter
, Bjorn Sunde
, Lindsay Flint
, Dean Thompson
, Thomas R. Ioerger
, Jim Sacchettini
, M. R.K. Alley
, Tanya Parish

Infectious Disease Research Institute
Pfizer
Texas A&M University

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

29 Citations (Scopus)

Abstract

We identified a series of novel 7-phenyl benzoxaborole compounds with activity against Mycobacterium tuberculosis. Compounds had a range of activity with inhibitory concentrations (IC₉₀) as low as 5.1 μM and no cytotoxicity against eukaryotic cells (IC₅₀ > 50 μM). Compounds were active against intracellular mycobacteria cultured in THP-1 macrophages. We isolated and characterized resistant mutants with mutations in NADH dehydrogenase (Ndh) or the regulatory protein Mce3R. Mutations suggest that Ndh may be the target of this series.

Original language	English
Pages (from-to)	96-98
Number of pages	3
Journal	Tuberculosis
Volume	108
Early online date	7 Nov 2017
DOIs	https://doi.org/10.1016/j.tube.2017.11.003
Publication status	Published - 1 Jan 2018
Externally published	Yes

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SDG 3 Good Health and Well-being

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10.1016/j.tube.2017.11.003Licence: CC BY

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title = "The 7-phenyl benzoxaborole series is active against Mycobacterium tuberculosis",

abstract = "We identified a series of novel 7-phenyl benzoxaborole compounds with activity against Mycobacterium tuberculosis. Compounds had a range of activity with inhibitory concentrations (IC90) as low as 5.1 μM and no cytotoxicity against eukaryotic cells (IC50 > 50 μM). Compounds were active against intracellular mycobacteria cultured in THP-1 macrophages. We isolated and characterized resistant mutants with mutations in NADH dehydrogenase (Ndh) or the regulatory protein Mce3R. Mutations suggest that Ndh may be the target of this series.",

author = "Aaron Korkegian and Theresa O'Malley and Yi Xia and Yasheen Zhou and Carter, \{David S.\} and Bjorn Sunde and Lindsay Flint and Dean Thompson and Ioerger, \{Thomas R.\} and Jim Sacchettini and Alley, \{M. R.K.\} and Tanya Parish",

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doi = "10.1016/j.tube.2017.11.003",

language = "English",

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TY - JOUR

T1 - The 7-phenyl benzoxaborole series is active against Mycobacterium tuberculosis

AU - Korkegian, Aaron

AU - O'Malley, Theresa

AU - Xia, Yi

AU - Zhou, Yasheen

AU - Carter, David S.

AU - Sunde, Bjorn

AU - Flint, Lindsay

AU - Thompson, Dean

AU - Ioerger, Thomas R.

AU - Sacchettini, Jim

AU - Alley, M. R.K.

AU - Parish, Tanya

PY - 2018/1/1

Y1 - 2018/1/1

N2 - We identified a series of novel 7-phenyl benzoxaborole compounds with activity against Mycobacterium tuberculosis. Compounds had a range of activity with inhibitory concentrations (IC90) as low as 5.1 μM and no cytotoxicity against eukaryotic cells (IC50 > 50 μM). Compounds were active against intracellular mycobacteria cultured in THP-1 macrophages. We isolated and characterized resistant mutants with mutations in NADH dehydrogenase (Ndh) or the regulatory protein Mce3R. Mutations suggest that Ndh may be the target of this series.

AB - We identified a series of novel 7-phenyl benzoxaborole compounds with activity against Mycobacterium tuberculosis. Compounds had a range of activity with inhibitory concentrations (IC90) as low as 5.1 μM and no cytotoxicity against eukaryotic cells (IC50 > 50 μM). Compounds were active against intracellular mycobacteria cultured in THP-1 macrophages. We isolated and characterized resistant mutants with mutations in NADH dehydrogenase (Ndh) or the regulatory protein Mce3R. Mutations suggest that Ndh may be the target of this series.

U2 - 10.1016/j.tube.2017.11.003

DO - 10.1016/j.tube.2017.11.003

M3 - Article

C2 - 29523334

AN - SCOPUS:85034416287

SN - 1472-9792

VL - 108

SP - 96

EP - 98

JO - Tuberculosis

JF - Tuberculosis

ER -

The 7-phenyl benzoxaborole series is active against Mycobacterium tuberculosis

Abstract

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