ArticlePLoS pathogens2020
New 2-Ethylthio-4-methylaminoquinazoline derivatives inhibiting two subunits of cytochrome bc1 in Mycobacterium tuberculosis.
Article in PLoS pathogens, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
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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.
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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
23 citing papers in PubMed, 57 citations in OpenAlex.
- The Mycobacterial cyt-Journal of medicinal chemistry · 2026Article
- A Series of Pyrazolo-Quinazoline Amines Inhibits the CytochromeJournal of medicinal chemistry · 2026Article
- Respiratory chain gene mutations associated with global phylogenetic clustering of drug-resistantFrontiers in immunology · 2026Article
- Reference-based chemical-genetic interaction profiling to elucidate small molecule mechanism of action in Mycobacterium tuberculosis.Nature communications · 2025Article
- Scaffold Hopping Strategy toward New 4‑Aminoquinazolines Active Against Extracellular and Intracellular.ACS medicinal chemistry letters · 2025Article
- Article
- Fighting Antimicrobial Resistance: Innovative Drugs in Antibacterial Research.Angewandte Chemie (International ed. in English) · 2025Review
- Structural and mechanistic study of a novel inhibitor analogue ofnpj drug discovery · 2025Article
- An open-access dashboard to interrogate the genetic diversity of Mycobacterium tuberculosis clinical isolates.Scientific reports · 2024Article
- Association of mutations in Mycobacterium tuberculosis complex (MTBC) respiration chain genes with hyper-transmission.BMC genomics · 2024Article
- Membrane depolarization kills dormant Bacillus subtilis cells by generating a lethal dose of ROS.Nature communications · 2024Article
- Review
- Telacebec Interferes with Virulence Lipid Biosynthesis Protein Expression and Sensitizes to Other Antibiotics.Microorganisms · 2023Article
- Target Identification in Anti-Tuberculosis Drug Discovery.International journal of molecular sciences · 2023Review
- Molecular Mechanisms of MmpL3 Function and Inhibition.Microbial drug resistance (Larchmont, N.Y.) · 2023Review
- Targeting the cytochrome bcMolecular diversity · 2022Review
- Structure ofeLife · 2021Article
- Article
- Nitric Oxide-Dependent Electron Transport Chain Inhibition by the CytochromeAntimicrobial agents and chemotherapy · 2021Article
- Article
Corrections and comments
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Authors and funding
12 authors at 6 institutions in 6 countries.
Funding
Abstract
The emergence of multi-drug (MDR-TB) and extensively-drug resistant tuberculosis (XDR-TB) is a major threat to the global management of tuberculosis (TB) worldwide. New chemical entities are of need to treat drug-resistant TB. In this study, the mode of action of new, potent quinazoline derivatives was investigated against Mycobacterium tuberculosis (M. tb). Four derivatives 11626141, 11626142, 11626252 and 11726148 showed good activity (MIC ranging from 0.02-0.09 μg/mL) and low toxicity (TD50 ≥ 5μg/mL) in vitro against M. tb strain H37Rv and HepG2 cells, respectively. 11626252 was the most selective compound from this series. Quinazoline derivatives were found to target cytochrome bc1 by whole-genome sequencing of mutants selected with 11626142. Two resistant mutants harboured the transversion T943G (Trp312Gly) and the transition G523A (Gly175Ser) in the cytochrome bc1 complex cytochrome b subunit (QcrB). Interestingly, a third mutant QuinR-M1 contained a mutation in the Rieske iron-sulphur protein (QcrA) leading to resistance to quinazoline and other QcrB inhibitors, the first report of cross-resistance involving QcrA. Modelling of both QcrA and QcrB revealed that all three resistance mutations are located in the stigmatellin pocket, as previously observed for other QcrB inhibitors such as Q203, AX-35, and lansoprazole sulfide (LPZs). Further analysis of the mode of action in vitro revealed that 11626252 exposure leads to ATP depletion, a decrease in the oxygen consumption rate and also overexpression of the cytochrome bd oxidase in M. tb. Our findings suggest that quinazoline-derived compounds are a new and attractive chemical entity for M. tb drug development targeting two separate subunits of the cytochrome bc1 complex.
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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.