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H1-NMR, EI-MS, and ESI-MS were performed to determine their molecular mass and elucidate their structures. Their size, zeta potential, size distribution, and polydispersity index (PDI) were assessed. Amoebicidal assays revealed that all the drugs and their nanoformulations, (except itraconazole) presented significant anti-amoebic effects against B. mandrillaris, while all the treatments indicated notable amoebicidal properties against N. fowleri. Amoebicidal effects were radically enhanced upon conjugating the drugs with nanoparticles. The IC50 values for KM-38-AgNPs-F, KM-20-AgNPs-M, and KM-IF were 65.09, 91.27, and 72.19\u2009\u00b5g.mL-1, respectively, against B. mandrillaris. Whereas against N. fowleri, the IC50 values were: 71.85, 73.95, and 63.01\u2009\u00b5g.mL-1, respectively. Additionally, nanoformulations significantly reduced N. fowleri-mediated host cell death, while nanoformulations along with fluconazole and metronidazole considerably reduced Balamuthia-mediated human cell damage. Finally, all the tested drugs and their nanoformulations revealed limited cytotoxic activity against human cerebral microvascular endothelial cell (HBEC-5i) cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These compounds should be developed into novel chemotherapeutic options for use against these distressing infections due to free-living amoebae, as currently there are no effective treatments.<\/jats:p><\/jats:sec>","DOI":"10.1093\/jambio\/lxad072","type":"journal-article","created":{"date-parts":[[2023,4,7]],"date-time":"2023-04-07T01:07:11Z","timestamp":1680829631000},"source":"Crossref","is-referenced-by-count":8,"title":["Azole and 5-nitroimidazole based nanoformulations are potential antiamoebic drug candidates against brain-eating amoebae"],"prefix":"10.1093","volume":"134","author":[{"given":"Noor","family":"Akbar","sequence":"first","affiliation":[{"name":"Research Institute of Medical & Health Sciences, University of Sharjah, University , Sharjah 27272 , Unites Arab Emirates"},{"name":"Department of Clinical Sciences, College of Medicine, University of Sharjah , Sharjah 27272 , Unites Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kashif","family":"Hussain","sequence":"additional","affiliation":[{"name":"H.E.J. Research Institute of Chemistry, International Centre for Chemical and Biological Sciences, University of Karachi , Karachi City, Sindh 75270 , Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Khalid","sequence":"additional","affiliation":[{"name":"H.E.J. Research Institute of Chemistry, International Centre for Chemical and Biological Sciences, University of Karachi , Karachi City, Sindh 75270 , Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruqaiyyah","family":"Siddiqui","sequence":"additional","affiliation":[{"name":"College of Arts and Sciences, American University of Sharjah, University City , Sharjah 26666 , United Arab Emirates"},{"name":"Department of Medical Biology, Faculty of Medicine, Istinye University , 34010 Istanbul , Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad Raza","family":"Shah","sequence":"additional","affiliation":[{"name":"H.E.J. 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