ArticlePloS one2014
Pentacyclic nitrofurans with in vivo efficacy and activity against nonreplicating Mycobacterium tuberculosis.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 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.
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
14 citing papers in PubMed.
- Advancing Tuberculosis Treatment with Next-Generation Drugs and Smart Delivery Systems.Pharmaceutics · 2026Review
- Intracellular and Extracellular Efficacy of Homoisoflavone Derivatives Against Mycobacterium Tuberculosis: Progress Toward Novel Antitubercular Agents.ChemMedChem · 2025Article
- Both Nitro Groups Are Essential for High Antitubercular Activity of 3,5-Dinitrobenzylsulfanyl Tetrazoles and 1,3,4-Oxadiazoles through the Deazaflavin-Dependent Nitroreductase Activation Pathway.Journal of medicinal chemistry · 2024Article
- Discovery and characterization of antimycobacterial nitro-containing compounds with distinct mechanisms of action andAntimicrobial agents and chemotherapy · 2023Article
- Evaluation of Acute and Sub-Acute Toxicity, Oxidative Stress and Molecular Docking of Two Nitrofuranyl Amides as Promising Anti-Tuberculosis Agents.Biomolecules · 2023Article
- SigH stress response mediates killing of Mycobacterium tuberculosis by activating nitronaphthofuran prodrugs via induction of Mrx2 expression.Nucleic acids research · 2023Article
- Potential anti-TB investigational compounds and drugs with repurposing potential in TB therapy: a conspectus.Applied microbiology and biotechnology · 2020Review
- A concise and sequential synthesis of the nitroimidazooxazole based drug, Delamanid and related compounds.RSC advances · 2020Article
- Optimization of N-benzyl-5-nitrofuran-2-carboxamide as an antitubercular agent.Bioorganic & medicinal chemistry letters · 2019Article
- 7-Substituted 2-Nitro-5,6-dihydroimidazo[2,1-b][1,3]oxazines: Novel Antitubercular Agents Lead to a New Preclinical Candidate for Visceral Leishmaniasis.Journal of medicinal chemistry · 2017Article
- Spectinamides are effective partner agents for the treatment of tuberculosis in multiple mouse infection models.The Journal of antimicrobial chemotherapy · 2017Article
- Targeting Phenotypically Tolerant Mycobacterium tuberculosis.Microbiology spectrum · 2017Review
- Pentacyclic nitrofurans that rapidly kill nifurtimox-resistant trypanosomes.The Journal of antimicrobial chemotherapy · 2016Article
- Nitrofuranyl Methyl Piperazines as New Anti-TB Agents: Identification, Validation, Medicinal Chemistry, and PK Studies.ACS medicinal chemistry letters · 2015Article
Corrections and comments
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Authors and funding
13 authors.
Funding
Abstract
The reductively activated nitroaromatic class of antimicrobials, which include nitroimidazole and the more metabolically labile nitrofuran antitubercular agents, have demonstrated some potential for development as therapeutics against dormant TB bacilli. In previous studies, the pharmacokinetic properties of nitrofuranyl isoxazolines were improved by incorporation of the outer ring elements of the antitubercular nitroimidazole OPC-67683. This successfully increased stability of the resulting pentacyclic nitrofuran lead compound Lee1106 (referred to herein as 9a). In the current study, we report the synthesis and antimicrobial properties of 9a and panel of 9a analogs, which were developed to increase oral bioavailability. These hybrid nitrofurans remained potent inhibitors of Mycobacterium tuberculosis with favorable selectivity indices (>150) and a narrow spectrum of activity. In vivo, the pentacyclic nitrofuran compounds showed long half-lives and high volumes of distribution. Based on pharmacokinetic testing and lack of toxicity in vivo, 9a remained the series lead. 9a exerted a lengthy post antibiotic effect and was highly active against nonreplicating M. tuberculosis grown under hypoxia. 9a showed a low potential for cross resistance to current antitubercular agents, and a mechanism of activation distinct from pre-clinical tuberculosis candidates PA-824 and OPC-67683. Together these studies show that 9a is a nanomolar inhibitor of actively growing as well as nonreplicating M. tuberculosis.
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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.