ArticlePloS one2019
Mechanism and resistance for antimycobacterial activity of a fluoroquinophenoxazine compound.
Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
10 citing papers in PubMed.
- Search for Specific Inhibitors Targeting Type IA Topoisomerases.Journal of molecular biology · 2026Review
- Current Advances in Developing New Antimicrobial Agents Against Non-TuberculousAntibiotics (Basel, Switzerland) · 2025Review
- Inhibition of DNA cleavage and strand passage activities of Mycobacterium tuberculosis topoisomerase I.Nucleic acids research · 2025Article
- Durlobactam to boost the clinical utility of standard of care β-lactams againstAntimicrobial agents and chemotherapy · 2025Article
- Rifampicin and isoniazid resistance not promote fluoroquinolone resistance in Mycobacterium smegmatis.PloS one · 2025Article
- Small Molecule Inhibitors ofInternational journal of molecular sciences · 2024Article
- Novel and Structurally Diversified Bacterial DNA Gyrase Inhibitors Discovered through a Fluorescence-Based High-Throughput Screening Assay.ACS pharmacology & translational science · 2022Article
- Pipeline of anti-Mycobacterium abscessus small molecules: Repurposable drugs and promising novel chemical entities.Medicinal research reviews · 2021Review
- Type IA Topoisomerases as Targets for Infectious Disease Treatments.Microorganisms · 2021Review
- Biofilms of the non-tuberculousCell surface (Amsterdam, Netherlands) · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors.
Funding
Abstract
We have previously reported the inhibition of bacterial topoisomerase I activity by a fluoroquinophenoxazine compound (FP-11g) with a 6-bipiperidinyl lipophilic side chain that exhibited promising antituberculosis activity (MIC = 2.5 μM against Mycobacterium tuberculosis, SI = 9.8). Here, we found that the compound is bactericidal towards Mycobacterium smegmatis, resulting in greater than 5 Log10 reduction in colony-forming units [cfu]/mL following a 10 h incubation at 1.25 μM (4X MIC) concentration. Growth inhibition (MIC = 50 μM) and reduction in cfu could also be observed against a clinical isolate of Mycobacterium abscessus. Stepwise isolation of resistant mutants of M. smegmatis was conducted to explore the mechanism of resistance. Mutations in the resistant isolates were identified by direct comparison of whole-genome sequencing data from mutant and wild-type isolates. These include mutations in genes likely to affect the entry and retention of the compound. FP-11g inhibits Mtb topoisomerase I and Mtb gyrase with IC50 of 0.24 and 27 μM, respectively. Biophysical analysis showed that FP-11g binds DNA as an intercalator but the IC50 for inhibition of Mtb topoisomerase I activity is >10 fold lower than the compound concentrations required for producing negatively supercoiled DNA during ligation of nicked circular DNA. Thus, the DNA-binding property of FP-11g may contribute to its antimycobacterial mechanism, but that alone cannot account for the observed inhibition of Mtb topoisomerase I.
Indexed as
Identifiers
What OpenQuestion holds
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.