ArticleThe Journal of antibiotics2015
Antimycobacterial activity of DNA intercalator inhibitors of Mycobacterium tuberculosis primase DnaG.
Article in The Journal of antibiotics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 45 citations in OpenAlex.
- Cefpiramide RestrictsACS medicinal chemistry letters · 2026Article
- In Silico and in vitro antiviral activity of FDA approved drugs from ZINC database against RNA-dependent RNA polymerase of dengue virus.Virology journal · 2026Article
- Integration of multi-modal measurements identifies critical mechanisms of tuberculosis drug action.Cell systems · 2025Article
- Development of tolerance to bedaquiline by overexpression of trypanosomal acetate: succinate CoA transferase in Mycobacterium smegmatis.Communications biology · 2025Article
- Antibacterial phenolic compounds from the flowering plants of Asia and the Pacific: coming to the light.Pharmaceutical biology · 2024Review
- Integrating bacterial molecular genetics with chemical biology for renewed antibacterial drug discovery.The Biochemical journal · 2024Review
- Inhibition of Replication Fork Formation and Progression: Targeting the Replication Initiation and Primosomal Proteins.International journal of molecular sciences · 2023Review
- Upcycling the anthracyclines: New mechanisms of action, toxicology, and pharmacology.Toxicology and applied pharmacology · 2023Review
- Article
- Anti-tubercular derivatives of rhein require activation by the monoglyceride lipase Rv0183.Cell surface (Amsterdam, Netherlands) · 2020Article
- Antimycobacterial activity of an anthracycline produced by an endophyte isolated from Amphipterygium adstringens.Molecular biology reports · 2018Article
- Inhibition of DNA replication in Staphylococcus aureus by tegaserod.The Journal of antibiotics · 2017Article
- Targeting DNA Replication and Repair for the Development of Novel Therapeutics against Tuberculosis.Frontiers in molecular biosciences · 2017Review
- Development of ebsulfur analogues as potent antibacterials against methicillin-resistant Staphylococcus aureus.Bioorganic & medicinal chemistry · 2016Article
- A biocatalytic approach to capuramycin analogues by exploiting a substrate permissive N-transacylase CapW.Organic & biomolecular chemistry · 2016Article
- Article
- A High Throughput Screening Assay for Anti-Mycobacterial Small Molecules Based on Adenylate Kinase Release as a Reporter of Cell Lysis.PloS one · 2015Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
Owing to the rise in drug resistance in tuberculosis combined with the global spread of its causative pathogen, Mycobacterium tuberculosis (Mtb), innovative anti mycobacterial agents are urgently needed. Recently, we developed a novel primase-pyrophosphatase assay and used it to discover inhibitors of an essential Mtb enzyme, primase DnaG (Mtb DnaG), a promising and unexplored potential target for novel antituberculosis chemotherapeutics. Doxorubicin, an anthracycline antibiotic used as an anticancer drug, was found to be a potent inhibitor of Mtb DnaG. In this study, we investigated both inhibition of Mtb DnaG and the inhibitory activity against in vitro growth of Mtb and M. smegmatis (Msm) by other anthracyclines, daunorubicin and idarubicin, as well as by less cytotoxic DNA intercalators: aloe-emodin, rhein and a mitoxantrone derivative. Generally, low-μM inhibition of Mtb DnaG by the anthracyclines was correlated with their low-μM minimum inhibitory concentrations. Aloe-emodin displayed threefold weaker potency than doxorubicin against Mtb DnaG and similar inhibition of Msm (but not Mtb) in the mid-μM range, whereas rhein (a close analog of aloe-emodin) and a di-glucosylated mitoxantrone derivative did not show significant inhibition of Mtb DnaG or antimycobacterial activity. Taken together, these observations strongly suggest that several clinically used anthracyclines and aloe-emodin target mycobacterial primase, setting the stage for a more extensive exploration of this enzyme as an antibacterial target.
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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.