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Discovery and Preliminary Structure-Activity Investigation of 3-Substituted-1H-imidazol-5-yl-1H-indoles with In Vitro Activity towards Methicillin-Resistant Staphylococcus aureus

Antibiotics have been the cornerstone of modern medicine saving lives by virtue of being able to cure infectious diseases and to prevent infections in those who are immune compromised. Their intense use has led to a surging increase in the incidence of antibiotic-resistant bacteria resulting in a de...

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Autores principales: Li, Steven A., Zheng, Rebecca J., Sue, Kenneth, Bourguet-Kondracki, Marie-Lise, Troudi, Azza, Brunel, Jean Michel, Copp, Brent R., Cadelis, Melissa M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9598367/
https://www.ncbi.nlm.nih.gov/pubmed/36290109
http://dx.doi.org/10.3390/antibiotics11101450
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author Li, Steven A.
Zheng, Rebecca J.
Sue, Kenneth
Bourguet-Kondracki, Marie-Lise
Troudi, Azza
Brunel, Jean Michel
Copp, Brent R.
Cadelis, Melissa M.
author_facet Li, Steven A.
Zheng, Rebecca J.
Sue, Kenneth
Bourguet-Kondracki, Marie-Lise
Troudi, Azza
Brunel, Jean Michel
Copp, Brent R.
Cadelis, Melissa M.
author_sort Li, Steven A.
collection PubMed
description Antibiotics have been the cornerstone of modern medicine saving lives by virtue of being able to cure infectious diseases and to prevent infections in those who are immune compromised. Their intense use has led to a surging increase in the incidence of antibiotic-resistant bacteria resulting in a desperate need for antibiotics with new mechanisms of action. As part of our search for new antimicrobials we have screened an in-house library of compounds and identified two 3-substituted-1H-imidazol-5-yl-1H-indoles as weak growth inhibitors (MIC 16 µg/mL) against methicillin-resistant Staphylococcus aureus (MRSA). An extensive library of analogues was prepared using the Van Leusen three-component reaction, biological evaluation of which led to the identification of two analogues (26 and 32) with favorable anti-MRSA activity (MIC ≤ 0.25 µg/mL) which also lacked cytotoxic or hemolytic properties. The screening campaign also identified two derivatives, a phenethyl-indole-imidazole 57 and a 5-phenyl-1H-imidazole 111 that were non-toxic selective antifungals towards Cryptococcus neoformans. These results have identified 3-substituted-1H-imidazol-5-yl-1H-indoles and 5-phenyl-1H-imidazoles as new structural scaffolds for further investigation as anti-MRSA and anti-C. neoformans agents, respectively.
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spelling pubmed-95983672022-10-27 Discovery and Preliminary Structure-Activity Investigation of 3-Substituted-1H-imidazol-5-yl-1H-indoles with In Vitro Activity towards Methicillin-Resistant Staphylococcus aureus Li, Steven A. Zheng, Rebecca J. Sue, Kenneth Bourguet-Kondracki, Marie-Lise Troudi, Azza Brunel, Jean Michel Copp, Brent R. Cadelis, Melissa M. Antibiotics (Basel) Article Antibiotics have been the cornerstone of modern medicine saving lives by virtue of being able to cure infectious diseases and to prevent infections in those who are immune compromised. Their intense use has led to a surging increase in the incidence of antibiotic-resistant bacteria resulting in a desperate need for antibiotics with new mechanisms of action. As part of our search for new antimicrobials we have screened an in-house library of compounds and identified two 3-substituted-1H-imidazol-5-yl-1H-indoles as weak growth inhibitors (MIC 16 µg/mL) against methicillin-resistant Staphylococcus aureus (MRSA). An extensive library of analogues was prepared using the Van Leusen three-component reaction, biological evaluation of which led to the identification of two analogues (26 and 32) with favorable anti-MRSA activity (MIC ≤ 0.25 µg/mL) which also lacked cytotoxic or hemolytic properties. The screening campaign also identified two derivatives, a phenethyl-indole-imidazole 57 and a 5-phenyl-1H-imidazole 111 that were non-toxic selective antifungals towards Cryptococcus neoformans. These results have identified 3-substituted-1H-imidazol-5-yl-1H-indoles and 5-phenyl-1H-imidazoles as new structural scaffolds for further investigation as anti-MRSA and anti-C. neoformans agents, respectively. MDPI 2022-10-21 /pmc/articles/PMC9598367/ /pubmed/36290109 http://dx.doi.org/10.3390/antibiotics11101450 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
Li, Steven A.
Zheng, Rebecca J.
Sue, Kenneth
Bourguet-Kondracki, Marie-Lise
Troudi, Azza
Brunel, Jean Michel
Copp, Brent R.
Cadelis, Melissa M.
Discovery and Preliminary Structure-Activity Investigation of 3-Substituted-1H-imidazol-5-yl-1H-indoles with In Vitro Activity towards Methicillin-Resistant Staphylococcus aureus
title Discovery and Preliminary Structure-Activity Investigation of 3-Substituted-1H-imidazol-5-yl-1H-indoles with In Vitro Activity towards Methicillin-Resistant Staphylococcus aureus
title_full Discovery and Preliminary Structure-Activity Investigation of 3-Substituted-1H-imidazol-5-yl-1H-indoles with In Vitro Activity towards Methicillin-Resistant Staphylococcus aureus
title_fullStr Discovery and Preliminary Structure-Activity Investigation of 3-Substituted-1H-imidazol-5-yl-1H-indoles with In Vitro Activity towards Methicillin-Resistant Staphylococcus aureus
title_full_unstemmed Discovery and Preliminary Structure-Activity Investigation of 3-Substituted-1H-imidazol-5-yl-1H-indoles with In Vitro Activity towards Methicillin-Resistant Staphylococcus aureus
title_short Discovery and Preliminary Structure-Activity Investigation of 3-Substituted-1H-imidazol-5-yl-1H-indoles with In Vitro Activity towards Methicillin-Resistant Staphylococcus aureus
title_sort discovery and preliminary structure-activity investigation of 3-substituted-1h-imidazol-5-yl-1h-indoles with in vitro activity towards methicillin-resistant staphylococcus aureus
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9598367/
https://www.ncbi.nlm.nih.gov/pubmed/36290109
http://dx.doi.org/10.3390/antibiotics11101450
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