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A Bioluminescence-Based Drug Screen Identifies Activities of Fexinidazole and Its Metabolites against Helicobacter pylori

Helicobacter pylori is responsible for a wide range of gastric diseases, including gastric cancer and gastritis. With half of the world’s population infected by H. pylori and the current standard of care associated with suboptimal outcomes, a search for more effective drugs is critical. To facilitat...

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Autores principales: Mohamed, Abdolhakim, Chilingerian, John N, Bali, Prerna, Obonyo, Marygorret, Debnath, Anjan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9686901/
https://www.ncbi.nlm.nih.gov/pubmed/36421252
http://dx.doi.org/10.3390/antibiotics11111605
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author Mohamed, Abdolhakim
Chilingerian, John N
Bali, Prerna
Obonyo, Marygorret
Debnath, Anjan
author_facet Mohamed, Abdolhakim
Chilingerian, John N
Bali, Prerna
Obonyo, Marygorret
Debnath, Anjan
author_sort Mohamed, Abdolhakim
collection PubMed
description Helicobacter pylori is responsible for a wide range of gastric diseases, including gastric cancer and gastritis. With half of the world’s population infected by H. pylori and the current standard of care associated with suboptimal outcomes, a search for more effective drugs is critical. To facilitate drug screening for H. pylori, we developed a microtiter plate-based compound screening method that is faster and can screen multiple compounds. We identified activities of fexinidazole and its sulfoxide and sulfone metabolites against H. pylori. Both fexinidazole and its metabolites exhibited equipotency against SS1, 60190, and G27 strains, which were about 3–6-fold more potent than the currently used metronidazole. We also determined the minimal inhibitory concentration (MIC) of metronidazole, fexinidazole, and its metabolites against these strains by a traditional agar plate-based method. While MIC values of fexinidazole and metronidazole were similar against all the strains, both sulfoxide and sulfone showed lower MIC values than metronidazole against SS1 and 60190. Given the recent FDA approval of fexinidazole, our data on the in vitro antibacterial activities of fexinidazole and its metabolites support further evaluation of this drug with the goal of producing an alternative nitro-based antimicrobial with good safety profiles for the treatment of H. pylori infection.
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spelling pubmed-96869012022-11-25 A Bioluminescence-Based Drug Screen Identifies Activities of Fexinidazole and Its Metabolites against Helicobacter pylori Mohamed, Abdolhakim Chilingerian, John N Bali, Prerna Obonyo, Marygorret Debnath, Anjan Antibiotics (Basel) Article Helicobacter pylori is responsible for a wide range of gastric diseases, including gastric cancer and gastritis. With half of the world’s population infected by H. pylori and the current standard of care associated with suboptimal outcomes, a search for more effective drugs is critical. To facilitate drug screening for H. pylori, we developed a microtiter plate-based compound screening method that is faster and can screen multiple compounds. We identified activities of fexinidazole and its sulfoxide and sulfone metabolites against H. pylori. Both fexinidazole and its metabolites exhibited equipotency against SS1, 60190, and G27 strains, which were about 3–6-fold more potent than the currently used metronidazole. We also determined the minimal inhibitory concentration (MIC) of metronidazole, fexinidazole, and its metabolites against these strains by a traditional agar plate-based method. While MIC values of fexinidazole and metronidazole were similar against all the strains, both sulfoxide and sulfone showed lower MIC values than metronidazole against SS1 and 60190. Given the recent FDA approval of fexinidazole, our data on the in vitro antibacterial activities of fexinidazole and its metabolites support further evaluation of this drug with the goal of producing an alternative nitro-based antimicrobial with good safety profiles for the treatment of H. pylori infection. MDPI 2022-11-11 /pmc/articles/PMC9686901/ /pubmed/36421252 http://dx.doi.org/10.3390/antibiotics11111605 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
Mohamed, Abdolhakim
Chilingerian, John N
Bali, Prerna
Obonyo, Marygorret
Debnath, Anjan
A Bioluminescence-Based Drug Screen Identifies Activities of Fexinidazole and Its Metabolites against Helicobacter pylori
title A Bioluminescence-Based Drug Screen Identifies Activities of Fexinidazole and Its Metabolites against Helicobacter pylori
title_full A Bioluminescence-Based Drug Screen Identifies Activities of Fexinidazole and Its Metabolites against Helicobacter pylori
title_fullStr A Bioluminescence-Based Drug Screen Identifies Activities of Fexinidazole and Its Metabolites against Helicobacter pylori
title_full_unstemmed A Bioluminescence-Based Drug Screen Identifies Activities of Fexinidazole and Its Metabolites against Helicobacter pylori
title_short A Bioluminescence-Based Drug Screen Identifies Activities of Fexinidazole and Its Metabolites against Helicobacter pylori
title_sort bioluminescence-based drug screen identifies activities of fexinidazole and its metabolites against helicobacter pylori
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9686901/
https://www.ncbi.nlm.nih.gov/pubmed/36421252
http://dx.doi.org/10.3390/antibiotics11111605
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