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Antiamoebic Properties of Laboratory and Clinically Used Drugs against Naegleria fowleri and Balamuthia mandrillaris

Naegleria fowleri and Balamuthia mandrillaris are pathogenic free-living amoebae that infect the central nervous system with over 95% mortality rates. Although several compounds have shown promise in vitro but associated side effects and/or prolonged approval processes for clinical applications have...

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Autores principales: Siddiqui, Ruqaiyyah, Mungroo, Mohammad Ridwane, Anuar, Tengku Shahrul, Alharbi, Ahmad M., Alfahemi, Hasan, Elmoselhi, Adel B., Khan, Naveed Ahmed
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9220410/
https://www.ncbi.nlm.nih.gov/pubmed/35740156
http://dx.doi.org/10.3390/antibiotics11060749
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author Siddiqui, Ruqaiyyah
Mungroo, Mohammad Ridwane
Anuar, Tengku Shahrul
Alharbi, Ahmad M.
Alfahemi, Hasan
Elmoselhi, Adel B.
Khan, Naveed Ahmed
author_facet Siddiqui, Ruqaiyyah
Mungroo, Mohammad Ridwane
Anuar, Tengku Shahrul
Alharbi, Ahmad M.
Alfahemi, Hasan
Elmoselhi, Adel B.
Khan, Naveed Ahmed
author_sort Siddiqui, Ruqaiyyah
collection PubMed
description Naegleria fowleri and Balamuthia mandrillaris are pathogenic free-living amoebae that infect the central nervous system with over 95% mortality rates. Although several compounds have shown promise in vitro but associated side effects and/or prolonged approval processes for clinical applications have led to limited success. To overcome this, drug repurposing of marketed compounds with known mechanism of action is considered a viable approach that has potential to expedite discovery and application of anti-amoebic compounds. In fact, many of the drugs currently employed in the treatment of N. fowleri and B. mandrillaris, such as amphotericin B, fluconazole, rifampin and miltefosine, are repurposed drugs. Here, we evaluated a range of clinical and laboratory compounds including metformin, quinclorac, indaziflam, inositol, nateglinide, 2,6-DNBT, trans-cinnamic acid, terbuthylazine, acarbose, glimepiride, vildagliptin, cellulase, thaxtomin A, repaglinide and dimethyl peptidase (IV) inhibitor against N. fowleri and B. mandrillaris. Anti-amoebic assays revealed that indaziflam, nateglinide, 2,6-DNBT, terbuthylazine, acarbose and glimepiride exhibited potent amoebicidal properties against both N. fowleri and B. mandrillaris. Notably, all compounds tested showed minimal human (HaCaT) cell cytotoxicity as determined by lactate dehydrogenase release. Prospective research using animal models is warranted to determine the potential of these repurposed compounds, as well as the need for investigating the intranasal route of delivery to treat these devastating infections.
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spelling pubmed-92204102022-06-24 Antiamoebic Properties of Laboratory and Clinically Used Drugs against Naegleria fowleri and Balamuthia mandrillaris Siddiqui, Ruqaiyyah Mungroo, Mohammad Ridwane Anuar, Tengku Shahrul Alharbi, Ahmad M. Alfahemi, Hasan Elmoselhi, Adel B. Khan, Naveed Ahmed Antibiotics (Basel) Article Naegleria fowleri and Balamuthia mandrillaris are pathogenic free-living amoebae that infect the central nervous system with over 95% mortality rates. Although several compounds have shown promise in vitro but associated side effects and/or prolonged approval processes for clinical applications have led to limited success. To overcome this, drug repurposing of marketed compounds with known mechanism of action is considered a viable approach that has potential to expedite discovery and application of anti-amoebic compounds. In fact, many of the drugs currently employed in the treatment of N. fowleri and B. mandrillaris, such as amphotericin B, fluconazole, rifampin and miltefosine, are repurposed drugs. Here, we evaluated a range of clinical and laboratory compounds including metformin, quinclorac, indaziflam, inositol, nateglinide, 2,6-DNBT, trans-cinnamic acid, terbuthylazine, acarbose, glimepiride, vildagliptin, cellulase, thaxtomin A, repaglinide and dimethyl peptidase (IV) inhibitor against N. fowleri and B. mandrillaris. Anti-amoebic assays revealed that indaziflam, nateglinide, 2,6-DNBT, terbuthylazine, acarbose and glimepiride exhibited potent amoebicidal properties against both N. fowleri and B. mandrillaris. Notably, all compounds tested showed minimal human (HaCaT) cell cytotoxicity as determined by lactate dehydrogenase release. Prospective research using animal models is warranted to determine the potential of these repurposed compounds, as well as the need for investigating the intranasal route of delivery to treat these devastating infections. MDPI 2022-05-31 /pmc/articles/PMC9220410/ /pubmed/35740156 http://dx.doi.org/10.3390/antibiotics11060749 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Siddiqui, Ruqaiyyah
Mungroo, Mohammad Ridwane
Anuar, Tengku Shahrul
Alharbi, Ahmad M.
Alfahemi, Hasan
Elmoselhi, Adel B.
Khan, Naveed Ahmed
Antiamoebic Properties of Laboratory and Clinically Used Drugs against Naegleria fowleri and Balamuthia mandrillaris
title Antiamoebic Properties of Laboratory and Clinically Used Drugs against Naegleria fowleri and Balamuthia mandrillaris
title_full Antiamoebic Properties of Laboratory and Clinically Used Drugs against Naegleria fowleri and Balamuthia mandrillaris
title_fullStr Antiamoebic Properties of Laboratory and Clinically Used Drugs against Naegleria fowleri and Balamuthia mandrillaris
title_full_unstemmed Antiamoebic Properties of Laboratory and Clinically Used Drugs against Naegleria fowleri and Balamuthia mandrillaris
title_short Antiamoebic Properties of Laboratory and Clinically Used Drugs against Naegleria fowleri and Balamuthia mandrillaris
title_sort antiamoebic properties of laboratory and clinically used drugs against naegleria fowleri and balamuthia mandrillaris
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9220410/
https://www.ncbi.nlm.nih.gov/pubmed/35740156
http://dx.doi.org/10.3390/antibiotics11060749
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