ArticleAntimicrobial agents and chemotherapy2015
Bis-benzimidazole hits against Naegleria fowleri discovered with new high-throughput screens.
Article in Antimicrobial agents and chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 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
24 citing papers in PubMed, 49 citations in OpenAlex.
- Development of dihydroquinazoline compounds as novel therapeutics against Naegleria fowleri.Bioorganic & medicinal chemistry letters · 2025Article
- Virulence ofbioRxiv : the preprint server for biology · 2025Article
- Nanoparticle-Terpene Fusion: A Game-Changer in Combating Primary Amoebic Meningoencephalitis Caused byACS omega · 2024Article
- Synthesis and Evaluation of Benzylamine Inhibitors of NeuropathogenicACS medicinal chemistry letters · 2024Article
- Identification of novel anti-amoebic pharmacophores from kinase inhibitor chemotypes.Frontiers in microbiology · 2023Article
- A Fluorometric Assay for theMicrobiology spectrum · 2022Article
- Polychlorinated cyclopentenes from a marine derived Periconia sp. (strain G1144).Phytochemistry · 2022Article
- Antiamoebic Properties of Metabolites againstAntibiotics (Basel, Switzerland) · 2022Article
- Opportunistic free-living amoebal pathogens.Pathogens and global health · 2022Article
- Differential Growth Rates andMicrobiology spectrum · 2022Article
- Various brain-eating amoebae: the protozoa, the pathogenesis, and the disease.Frontiers of medicine · 2021Review
- The therapeutic potential of novel isobenzofuranones against Naegleria fowleri.International journal for parasitology. Drugs and drug resistance · 2021Article
- Drug discovery for primary amebic meningoencephalitis: from screen to identification of leads.Expert review of anti-infective therapy · 2021Article
- EdU Incorporation To Assess Cell Proliferation and Drug Susceptibility in Naegleria fowleri.Antimicrobial agents and chemotherapy · 2021Article
- Discovery of repurposing drug candidates for the treatment of diseases caused by pathogenic free-living amoebae.PLoS neglected tropical diseases · 2020Article
- Antiamoebic activity of 3-aryl-6,7-dimethoxyquinazolin-4(3H)-one library against Acanthamoeba castellanii.Parasitology research · 2020Article
- Discovery of Anti-Amoebic Inhibitors from Screening the MMV Pandemic Response Box onPathogens (Basel, Switzerland) · 2020Article
- Article
- In Vitro Activity of Statins againstPathogens (Basel, Switzerland) · 2019Article
- Phenotypic Screens Reveal Posaconazole as a Rapidly Acting Amebicidal Combination Partner for Treatment of Primary Amoebic Meningoencephalitis.The Journal of infectious diseases · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Naegleria fowleri is a pathogenic free-living amoeba (FLA) that causes an acute fatal disease known as primary amoebic meningoencephalitis (PAM). The major problem for infections with any pathogenic FLA is a lack of effective therapeutics, since PAM has a case mortality rate approaching 99%. Clearly, new drugs that are potent and have rapid onset of action are needed to enhance the treatment regimens for PAM. Diamidines have demonstrated potency against multiple pathogens, including FLA, and are known to cross the blood-brain barrier to cure other protozoan diseases of the central nervous system. Therefore, amidino derivatives serve as an important chemotype for discovery of new drugs. In this study, we validated two new in vitro assays suitable for medium- or high-throughput drug discovery and used these for N. fowleri. We next screened over 150 amidino derivatives of multiple structural classes and identified two hit series with nM potency that are suitable for further lead optimization as new drugs for this neglected disease. These include both mono- and diamidino derivatives, with the most potent compound (DB173) having a 50% inhibitory concentration (IC50) of 177 nM. Similarly, we identified 10 additional analogues with IC50s of <1 μM, with many of these having reasonable selectivity indices. The most potent hits were >500 times more potent than pentamidine. In summary, the mono- and diamidino derivatives offer potential for lead optimization to develop new drugs to treat central nervous system infections with N. fowleri.
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.