Benzimidazole-based antibacterial agents against Francisella tularensis

Kunal Kumar; Divya Awasthi; Seung Yub Lee; Jason E. Cummings; Susan E. Knudson; Richard A. Slayden; Iwao Ojima

doi:10.1016/j.bmc.2013.02.059

Benzimidazole-based antibacterial agents against Francisella tularensis

Kunal Kumar
, Divya Awasthi
, Seung Yub Lee
, Jason E. Cummings
, Susan E. Knudson
, Richard A. Slayden
, Iwao Ojima

Chemistry

Stony Brook University
Colorado State University

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

44 Scopus citations

Abstract

Francisella tularensis is a highly virulent pathogenic bacterium. In order to identify novel potential antibacterial agents against F. tularensis, libraries of trisubstituted benzimidazoles were screened against F. tularensis LVS strain. In a preliminary screening assay, remarkably, 23 of 2,5,6- and 2,5,7-trisubstituted benzimidazoles showed excellent activity exhibiting greater than 90% growth inhibition at 1 μg/mL. Among those hits, 21 compounds showed MIC₉₀ values in the range of 0.35-48.6 μg/mL after accurate MIC determination. In ex vivo efficacy assays, four of these compounds exhibited 2-3 log reduction in colony forming units (CFU) per mL at concentrations of 10 and 50 μg/mL.

Original language	English
Pages (from-to)	3318-3326
Number of pages	9
Journal	Bioorganic and Medicinal Chemistry
Volume	21
Issue number	11
DOIs	https://doi.org/10.1016/j.bmc.2013.02.059
State	Published - Jun 1 2013

Keywords

Antibacterial
Benzimidazole
Francisella tularensis

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10.1016/j.bmc.2013.02.059

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title = "Benzimidazole-based antibacterial agents against Francisella tularensis",

abstract = "Francisella tularensis is a highly virulent pathogenic bacterium. In order to identify novel potential antibacterial agents against F. tularensis, libraries of trisubstituted benzimidazoles were screened against F. tularensis LVS strain. In a preliminary screening assay, remarkably, 23 of 2,5,6- and 2,5,7-trisubstituted benzimidazoles showed excellent activity exhibiting greater than 90\% growth inhibition at 1 μg/mL. Among those hits, 21 compounds showed MIC90 values in the range of 0.35-48.6 μg/mL after accurate MIC determination. In ex vivo efficacy assays, four of these compounds exhibited 2-3 log reduction in colony forming units (CFU) per mL at concentrations of 10 and 50 μg/mL.",

keywords = "Antibacterial, Benzimidazole, Francisella tularensis",

author = "Kunal Kumar and Divya Awasthi and Lee, \{Seung Yub\} and Cummings, \{Jason E.\} and Knudson, \{Susan E.\} and Slayden, \{Richard A.\} and Iwao Ojima",

year = "2013",

month = jun,

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doi = "10.1016/j.bmc.2013.02.059",

language = "English",

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journal = "Bioorganic and Medicinal Chemistry",

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TY - JOUR

T1 - Benzimidazole-based antibacterial agents against Francisella tularensis

AU - Kumar, Kunal

AU - Awasthi, Divya

AU - Lee, Seung Yub

AU - Cummings, Jason E.

AU - Knudson, Susan E.

AU - Slayden, Richard A.

AU - Ojima, Iwao

PY - 2013/6/1

Y1 - 2013/6/1

N2 - Francisella tularensis is a highly virulent pathogenic bacterium. In order to identify novel potential antibacterial agents against F. tularensis, libraries of trisubstituted benzimidazoles were screened against F. tularensis LVS strain. In a preliminary screening assay, remarkably, 23 of 2,5,6- and 2,5,7-trisubstituted benzimidazoles showed excellent activity exhibiting greater than 90% growth inhibition at 1 μg/mL. Among those hits, 21 compounds showed MIC90 values in the range of 0.35-48.6 μg/mL after accurate MIC determination. In ex vivo efficacy assays, four of these compounds exhibited 2-3 log reduction in colony forming units (CFU) per mL at concentrations of 10 and 50 μg/mL.

AB - Francisella tularensis is a highly virulent pathogenic bacterium. In order to identify novel potential antibacterial agents against F. tularensis, libraries of trisubstituted benzimidazoles were screened against F. tularensis LVS strain. In a preliminary screening assay, remarkably, 23 of 2,5,6- and 2,5,7-trisubstituted benzimidazoles showed excellent activity exhibiting greater than 90% growth inhibition at 1 μg/mL. Among those hits, 21 compounds showed MIC90 values in the range of 0.35-48.6 μg/mL after accurate MIC determination. In ex vivo efficacy assays, four of these compounds exhibited 2-3 log reduction in colony forming units (CFU) per mL at concentrations of 10 and 50 μg/mL.

KW - Antibacterial

KW - Benzimidazole

KW - Francisella tularensis

UR - https://www.scopus.com/pages/publications/84877808769

U2 - 10.1016/j.bmc.2013.02.059

DO - 10.1016/j.bmc.2013.02.059

M3 - Article

C2 - 23623254

AN - SCOPUS:84877808769

SN - 0968-0896

VL - 21

SP - 3318

EP - 3326

JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

IS - 11

ER -

Benzimidazole-based antibacterial agents against Francisella tularensis

Abstract

Keywords

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