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Imidazole-Thiosemicarbazide Derivatives as Potent Anti-Mycobacterium tuberculosis Compounds with Antibiofilm Activity

Mycobacterium tuberculosis (Mtb) is an intracellular pathogenic bacterium and the causative agent of tuberculosis. This disease is one of the most ancient and deadliest bacterial infections, as it poses major health, social and economic challenges at a global level, primarily in low- and middle-inco...

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Autores principales: Bekier, Adrian, Kawka, Malwina, Lach, Jakub, Dziadek, Jarosław, Paneth, Agata, Gatkowska, Justyna, Dzitko, Katarzyna, Dziadek, Bożena
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8700351/
https://www.ncbi.nlm.nih.gov/pubmed/34943984
http://dx.doi.org/10.3390/cells10123476
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author Bekier, Adrian
Kawka, Malwina
Lach, Jakub
Dziadek, Jarosław
Paneth, Agata
Gatkowska, Justyna
Dzitko, Katarzyna
Dziadek, Bożena
author_facet Bekier, Adrian
Kawka, Malwina
Lach, Jakub
Dziadek, Jarosław
Paneth, Agata
Gatkowska, Justyna
Dzitko, Katarzyna
Dziadek, Bożena
author_sort Bekier, Adrian
collection PubMed
description Mycobacterium tuberculosis (Mtb) is an intracellular pathogenic bacterium and the causative agent of tuberculosis. This disease is one of the most ancient and deadliest bacterial infections, as it poses major health, social and economic challenges at a global level, primarily in low- and middle-income countries. The lack of an effective vaccine, the long and expensive drug therapy, and the rapid spread of drug-resistant strains of Mtb have led to the re-emergence of tuberculosis as a global pandemic. Here, we assessed the in vitro activity of new imidazole-thiosemicarbazide derivatives (ITDs) against Mtb infection and their effects on mycobacterial biofilm formation. Cytotoxicity studies of the new compounds in cell lines and human monocyte-derived macrophages (MDMs) were performed. The anti-Mtb activity of ITDs was evaluated by determining minimal inhibitory concentrations of resazurin, time-kill curves, bacterial intracellular growth and the effect on biofilm formation. Mutation frequency and whole-genome sequencing of mutants that were resistant to ITDs were performed. The antimycobacterial potential of ITDs with the ability to penetrate Mtb-infected human macrophages and significantly inhibit the intracellular growth of tubercle bacilli and suppress Mtb biofilm formation was observed.
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spelling pubmed-87003512021-12-24 Imidazole-Thiosemicarbazide Derivatives as Potent Anti-Mycobacterium tuberculosis Compounds with Antibiofilm Activity Bekier, Adrian Kawka, Malwina Lach, Jakub Dziadek, Jarosław Paneth, Agata Gatkowska, Justyna Dzitko, Katarzyna Dziadek, Bożena Cells Article Mycobacterium tuberculosis (Mtb) is an intracellular pathogenic bacterium and the causative agent of tuberculosis. This disease is one of the most ancient and deadliest bacterial infections, as it poses major health, social and economic challenges at a global level, primarily in low- and middle-income countries. The lack of an effective vaccine, the long and expensive drug therapy, and the rapid spread of drug-resistant strains of Mtb have led to the re-emergence of tuberculosis as a global pandemic. Here, we assessed the in vitro activity of new imidazole-thiosemicarbazide derivatives (ITDs) against Mtb infection and their effects on mycobacterial biofilm formation. Cytotoxicity studies of the new compounds in cell lines and human monocyte-derived macrophages (MDMs) were performed. The anti-Mtb activity of ITDs was evaluated by determining minimal inhibitory concentrations of resazurin, time-kill curves, bacterial intracellular growth and the effect on biofilm formation. Mutation frequency and whole-genome sequencing of mutants that were resistant to ITDs were performed. The antimycobacterial potential of ITDs with the ability to penetrate Mtb-infected human macrophages and significantly inhibit the intracellular growth of tubercle bacilli and suppress Mtb biofilm formation was observed. MDPI 2021-12-09 /pmc/articles/PMC8700351/ /pubmed/34943984 http://dx.doi.org/10.3390/cells10123476 Text en © 2021 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
Bekier, Adrian
Kawka, Malwina
Lach, Jakub
Dziadek, Jarosław
Paneth, Agata
Gatkowska, Justyna
Dzitko, Katarzyna
Dziadek, Bożena
Imidazole-Thiosemicarbazide Derivatives as Potent Anti-Mycobacterium tuberculosis Compounds with Antibiofilm Activity
title Imidazole-Thiosemicarbazide Derivatives as Potent Anti-Mycobacterium tuberculosis Compounds with Antibiofilm Activity
title_full Imidazole-Thiosemicarbazide Derivatives as Potent Anti-Mycobacterium tuberculosis Compounds with Antibiofilm Activity
title_fullStr Imidazole-Thiosemicarbazide Derivatives as Potent Anti-Mycobacterium tuberculosis Compounds with Antibiofilm Activity
title_full_unstemmed Imidazole-Thiosemicarbazide Derivatives as Potent Anti-Mycobacterium tuberculosis Compounds with Antibiofilm Activity
title_short Imidazole-Thiosemicarbazide Derivatives as Potent Anti-Mycobacterium tuberculosis Compounds with Antibiofilm Activity
title_sort imidazole-thiosemicarbazide derivatives as potent anti-mycobacterium tuberculosis compounds with antibiofilm activity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8700351/
https://www.ncbi.nlm.nih.gov/pubmed/34943984
http://dx.doi.org/10.3390/cells10123476
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