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Antimycobacterial activity against Mycobacterium bovis BCG ATCC 35734 carrying katG loss-of-function mutant assessed fold reduction in MIC at 1 to 2 times of MIC90 incubated for 5 days

PubChem AID
1782239
Primary Citation
Functionalized Dioxonaphthoimidazoliums: A Redox Cycling Chemotype with Potent Bactericidal Activities against Mycobacterium tuberculosis [PMID: 34706190]
Source
External ID
Tested Substances
Tested Compounds
Version
Status
Live
Dates
  • Deposit:
    2022-08-30
  • Modify:
    2024-05-03
Description
This bioassay record (AID 1782239) reports results from the above primary citation. Additional data from the same publication are reported in a total of 51 BioAssay records in PubChem.

1 Description

Title: Functionalized Dioxonaphthoimidazoliums: A Redox Cycling Chemotype with Potent Bactericidal Activities against Mycobacterium tuberculosis.

Abstract: Disruption of redox homeostasis in mycobacteria causes irreversible stress induction and cell death. Here, we report the dioxonaphthoimidazolium scaffold as a novel redox cycling antituberculosis chemotype with potent bactericidal activity against growing and nutrient-starved phenotypically drug-resistant nongrowing bacteria. Maximal potency was dependent on the activation of the redox cycling quinone by the positively charged scaffold and accessibility to the mycobacterial cell membrane as directed by the lipophilicity and conformational characteristics of the N-substituted side chains. Evidence from microbiological, biochemical, and genetic investigations implicates a redox-driven mode of action that is reliant on the reduction of the quinone by type II NADH dehydrogenase (NDH2) for the generation of bactericidal levels of the reactive oxygen species (ROS). The bactericidal profile of a potent water-soluble analogue 32 revealed good activity against nutrient-starved organisms in the Loebel model of dormancy, low spontaneous resistance mutation frequency, and synergy with isoniazid in the checkerboard assay.

2 Comment

Journal: J Med Chem

Year: 2021

Volume: 64

Issue: 21.0

First Page: 15991

Last Page: 16007

DOI: 10.1021/acs.jmedchem.1c01383

Target ChEMBL ID: CHEMBL615052

ChEMBL Target Name: Mycobacterium tuberculosis variant bovis BCG

ChEMBL Target Type: ORGANISM - Target is a complete organism

Relationship Type: N - Non-molecular target assigned

Confidence: Target assigned is non-molecular

3 Result Definitions

4 Data Table

5 Target

7 Identity

7.1 BioAssay Name

Antimycobacterial activity against Mycobacterium bovis BCG ATCC 35734 carrying katG loss-of-function mutant assessed fold reduction in MIC at 1 to 2 times of MIC90 incubated for 5 days

7.2 Source

7.3 External ID

7.4 Project Category

Literature, Extracted

7.5 Deposit Date

2022-08-30

7.6 Modify Date

Version 1.1
Version 1.2
2024-05-03 (currently shown)

7.7 Status

Live

8 Same-Publication BioAssays

9 BioAssay Annotations

Assay Format
Organism-based
Assay Type
Functional
Assay Strain
ATCC 35734

10 Information Sources

  1. PubChem
  2. ChEMBL
    LICENSE
    Access to the web interface of ChEMBL is made under the EBI's Terms of Use (http://www.ebi.ac.uk/Information/termsofuse.html). The ChEMBL data is made available on a Creative Commons Attribution-Share Alike 3.0 Unported License (http://creativecommons.org/licenses/by-sa/3.0/).
    http://www.ebi.ac.uk/Information/termsofuse.html
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