ArticleJournal of biomolecular screening2009
Dequalinium, a new inhibitor of Mycobacterium tuberculosis mycothiol ligase identified by high-throughput screening.
Article in Journal of biomolecular screening, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
16 citing papers in PubMed, 47 citations in OpenAlex.
- Pharmacological targeting of the mycothiol cysteine ligase MshC in Mycobacteriumabscessus.The Journal of biological chemistry · 2026Article
- Structural Basis of Cysteine Ligase MshC Inhibition by Cysteinyl-Sulfonamides.International journal of molecular sciences · 2022Article
- Advances in Key Drug Target Identification and New Drug Development for Tuberculosis.BioMed research international · 2022Review
- Genome-wide identification of essential genes in Mycobacterium intracellulare by transposon sequencing - Implication for metabolic remodeling.Scientific reports · 2020Article
- A high-throughput whole cell screen to identify inhibitors of Mycobacterium tuberculosis.PloS one · 2019Article
- Host-pathogen redox dynamics modulate Mycobacterium tuberculosis pathogenesis.Pathogens and disease · 2018Article
- Compounds with Potential Activity against Mycobacterium tuberculosis.Antimicrobial agents and chemotherapy · 2018Article
- Construction and Characterization of a Recombinant Human Respiratory Syncytial Virus Encoding Enhanced Green Fluorescence Protein for Antiviral Drug Screening Assay.BioMed research international · 2018Article
- Reengineering redox sensitive GFP to measure mycothiol redox potential of Mycobacterium tuberculosis during infection.PLoS pathogens · 2014Article
- New targets and inhibitors of mycobacterial sulfur metabolism.Infectious disorders drug targets · 2013Review
- Examination of mechanism of N-acetyl-1-D-myo-inosityl-2-amino-2-deoxy-α-D-glucopyranoside deacetylase (MshB) reveals unexpected role for dynamic tyrosine.The Journal of biological chemistry · 2012Article
- Adenylating enzymes in Mycobacterium tuberculosis as drug targets.Current topics in medicinal chemistry · 2012Review
- Synergistic drug combinations for tuberculosis therapy identified by a novel high-throughput screen.Antimicrobial agents and chemotherapy · 2011Article
- Evaluation of NTF1836 as an inhibitor of the mycothiol biosynthetic enzyme MshC in growing and non-replicating Mycobacterium tuberculosis.Bioorganic & medicinal chemistry · 2011Article
- The activity and cofactor preferences of N-acetyl-1-D-myo-inosityl-2-amino-2-deoxy-alpha-D-glucopyranoside deacetylase (MshB) change depending on environmental conditions.The Journal of biological chemistry · 2011Article
- Susceptibility and mode of binding of the Mycobacterium tuberculosis cysteinyl transferase mycothiol ligase to tRNA synthetase inhibitors.Bioorganic & medicinal chemistry letters · 2011Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Mycothiol ligase (MshC) is a key enzyme in the biosynthesis of mycothiol, a small molecular weight thiol that is unique to actinomycetes and whose primary role is to maintain intracellular redox balance and remove toxins. MshC catalyzes the adenosine triphosphate (ATP)-dependent condensation of cysteine and glucosamine-inositol (GI) to produce cysteine-glucosamine-inositol (CGI). MshC is essential to Mycobacterium tuberculosis and therefore represents an attractive target for chemotherapeutic intervention. A screening protocol was developed to identify MshC inhibitors based on quantification of residual ATP using a coupled luminescent assay. The protocol was used to screen a library of 3100 compounds in a 384-well plate format (Z'>or=0.65). Fifteen hits (0.48%) were identified from the screen, and 2 hits were confirmed in a secondary assay that measures production of CGI. The structures of both hits contain N-substituted quinolinium moieties, and the more potent of the 2-namely, dequalinium chloride-inhibits MshC with an IC50 value of 24+/-1 microM. Further studies showed dequalinium to be an ATP-competitive inhibitor of MshC, to bind MshC with a KD of 0.22 microM, and to inhibit the growth of M. tuberculosis under aerobic and anaerobic conditions with minimum inhibitory and anaerobic bactericidal concentrations of 1.2 and 0.3 microg/mL, respectively. The screening protocol described is robust and has enabled the identification of new MshC inhibitors.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.