and are protist pathogens that infect the central nervous system, causing primary amoebic meningoencephalitis and granulomatous amoebic encephalitis with mortality rates of over 95%. Quinazolinones and their derivatives possess a wide spectrum of biological properties, but their antiamoebic effects against brain-eating amoebae have never been tested before. In this study, we synthesized a variety of 34 novel arylquinazolinones derivatives (Q1-Q34) by altering both quinazolinone core and aryl substituents. To study the antiamoebic activity of these synthetic arylquinazolinones, amoebicidal and amoebistatic assays were performed against and . Moreover, amoebae-mediated host cells cytotopathogenicity and cytotoxicity assays were performed against human keratinocytes cells . The results revealed that selected arylquinazolinones derivatives decreased the viability of and significantly ( < 0.05) and reduced cytopathogenicity of both parasites. Furthermore, these compounds were also found to be least cytotoxic against HaCat cells. Considering that nanoparticle-based materials possess potent activity against brain-eating amoebae, we conjugated quinazolinones derivatives with silver nanoparticles and showed that activities of the drugs were enhanced successfully after conjugation. The current study suggests that quinazolinones alone as well as conjugated with silver nanoparticles may serve as potent therapeutics against brain-eating amoebae.
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http://dx.doi.org/10.1021/acschemneuro.9b00596 | DOI Listing |
Mol Phylogenet Evol
January 2025
Charles University, Faculty of Science, Department of Zoology, Prague, Czechia.
The phylum Heterolobosea Page and Blanton, 1985 is a group of eukaryotes that contains heterotrophic flagellates, amoebae, and amoeboflagellates, including the infamous brain-eating amoeba Naegleria fowleri. In this study, we investigate the deep evolutionary history of Heterolobosea by generating and analyzing transcriptome data from 16 diverse isolates and combine this with previously published data in a comprehensive phylogenomic analysis. This dataset has representation of all but one of the major lineages classified here as orders.
View Article and Find Full Text PDFFront Cell Infect Microbiol
January 2025
Department of Biomedical Science and Technology, School of Biological Sciences, Ramakrishna Mission Vivekananda Educational and Research Institute (RKMVERI), Kolkata, India.
Amoebae, fascinatingly diverse protists, showcase a dual nature that positions them as both friends and foes in our world. These organisms, defined by their distinctive pseudopodia, span a spectrum from harmful to helpful. On the darker side, species like pose serious health risks, causing intestinal and liver diseases, while the infamous "brain-eating" leads to fatal primary amoebic meningoencephalitis (PAM), with a daunting 97% mortality rate.
View Article and Find Full Text PDFFront Cell Infect Microbiol
December 2024
Institut Pasteur de la Guadeloupe, Les Abymes, Guadeloupe, France.
The free-living amoeba (NF) causes a rare but lethal parasitic meningoencephalitis (PAM) in humans. Currently, this disease lacks effective treatments and the specific molecular mechanisms that govern NF pathogenesis and host brain response remain unknown. To address some of these issues, we sought to explore naturally existing virulence diversity within environmental NF isolates.
View Article and Find Full Text PDFMicrob Pathog
February 2025
Diamond Harbour Women's University, Department of Zoology, Sarisha, West Bengal, 743368, India. Electronic address:
Naegleria fowleri, is the causative agent of Primary Amoebic Meningoencephalitis (PAM), a lethal acute brain inflammation with high mortality. The virulent and reproductively active trophozoite stage of N. fowleri migrates to central nervous system (CNS) by entering through nasal passage and causes severe neural infection, brain disease and inflammation with high mortality.
View Article and Find Full Text PDFFront Med (Lausanne)
November 2024
Department of Neurology, The Second Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, Guangzhou, China.
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