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Synthesis of Novel Benzenesulfonamide-Bearing Functionalized Imidazole Derivatives as Novel Candidates Targeting Multidrug-Resistant Mycobacterium abscessus Complex

Infections caused by drug-resistant (DR) Mycobacterium abscessus (M. abscessus) complex (MAC) are an important public health concern, particularly when affecting individuals with various immunodeficiencies or chronic pulmonary diseases. Rapidly growing antimicrobial resistance among MAC urges us to...

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Autores principales: Balandis, Benas, Kavaliauskas, Povilas, Grybaitė, Birutė, Petraitis, Vidmantas, Petraitienė, Rūta, Naing, Ethan, Garcia, Andrew, Grigalevičiūtė, Ramunė, Mickevičius, Vytautas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10145568/
https://www.ncbi.nlm.nih.gov/pubmed/37110358
http://dx.doi.org/10.3390/microorganisms11040935
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author Balandis, Benas
Kavaliauskas, Povilas
Grybaitė, Birutė
Petraitis, Vidmantas
Petraitienė, Rūta
Naing, Ethan
Garcia, Andrew
Grigalevičiūtė, Ramunė
Mickevičius, Vytautas
author_facet Balandis, Benas
Kavaliauskas, Povilas
Grybaitė, Birutė
Petraitis, Vidmantas
Petraitienė, Rūta
Naing, Ethan
Garcia, Andrew
Grigalevičiūtė, Ramunė
Mickevičius, Vytautas
author_sort Balandis, Benas
collection PubMed
description Infections caused by drug-resistant (DR) Mycobacterium abscessus (M. abscessus) complex (MAC) are an important public health concern, particularly when affecting individuals with various immunodeficiencies or chronic pulmonary diseases. Rapidly growing antimicrobial resistance among MAC urges us to develop novel antimicrobial candidates for future optimization. Therefore, we have designed and synthesized benzenesulfonamide-bearing functionalized imidazole or S-alkylated derivatives and evaluated their antimicrobial activity using multidrug-resistant M. abscessus strains and compared their antimycobacterial activity using M. bovis BCG and M. tuberculosis H37Ra. Benzenesulfonamide-bearing imidazole-2-thiol compound 13, containing 4-CF(3) substituent in benzene ring, showed strong antimicrobial activity against the tested mycobacterial strains and was more active than some antibiotics used as a reference. Furthermore, an imidazole-bearing 4-F substituent and S-methyl group demonstrated good antimicrobial activity against M. abscessus complex strains, as well as M. bovis BCG and M. tuberculosis H37Ra. In summary, these results demonstrated that novel benzenesulfonamide derivatives, bearing substituted imidazoles, could be further explored as potential candidates for the further hit-to-lead optimization of novel antimycobacterial compounds.
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spelling pubmed-101455682023-04-29 Synthesis of Novel Benzenesulfonamide-Bearing Functionalized Imidazole Derivatives as Novel Candidates Targeting Multidrug-Resistant Mycobacterium abscessus Complex Balandis, Benas Kavaliauskas, Povilas Grybaitė, Birutė Petraitis, Vidmantas Petraitienė, Rūta Naing, Ethan Garcia, Andrew Grigalevičiūtė, Ramunė Mickevičius, Vytautas Microorganisms Article Infections caused by drug-resistant (DR) Mycobacterium abscessus (M. abscessus) complex (MAC) are an important public health concern, particularly when affecting individuals with various immunodeficiencies or chronic pulmonary diseases. Rapidly growing antimicrobial resistance among MAC urges us to develop novel antimicrobial candidates for future optimization. Therefore, we have designed and synthesized benzenesulfonamide-bearing functionalized imidazole or S-alkylated derivatives and evaluated their antimicrobial activity using multidrug-resistant M. abscessus strains and compared their antimycobacterial activity using M. bovis BCG and M. tuberculosis H37Ra. Benzenesulfonamide-bearing imidazole-2-thiol compound 13, containing 4-CF(3) substituent in benzene ring, showed strong antimicrobial activity against the tested mycobacterial strains and was more active than some antibiotics used as a reference. Furthermore, an imidazole-bearing 4-F substituent and S-methyl group demonstrated good antimicrobial activity against M. abscessus complex strains, as well as M. bovis BCG and M. tuberculosis H37Ra. In summary, these results demonstrated that novel benzenesulfonamide derivatives, bearing substituted imidazoles, could be further explored as potential candidates for the further hit-to-lead optimization of novel antimycobacterial compounds. MDPI 2023-04-03 /pmc/articles/PMC10145568/ /pubmed/37110358 http://dx.doi.org/10.3390/microorganisms11040935 Text en © 2023 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
Balandis, Benas
Kavaliauskas, Povilas
Grybaitė, Birutė
Petraitis, Vidmantas
Petraitienė, Rūta
Naing, Ethan
Garcia, Andrew
Grigalevičiūtė, Ramunė
Mickevičius, Vytautas
Synthesis of Novel Benzenesulfonamide-Bearing Functionalized Imidazole Derivatives as Novel Candidates Targeting Multidrug-Resistant Mycobacterium abscessus Complex
title Synthesis of Novel Benzenesulfonamide-Bearing Functionalized Imidazole Derivatives as Novel Candidates Targeting Multidrug-Resistant Mycobacterium abscessus Complex
title_full Synthesis of Novel Benzenesulfonamide-Bearing Functionalized Imidazole Derivatives as Novel Candidates Targeting Multidrug-Resistant Mycobacterium abscessus Complex
title_fullStr Synthesis of Novel Benzenesulfonamide-Bearing Functionalized Imidazole Derivatives as Novel Candidates Targeting Multidrug-Resistant Mycobacterium abscessus Complex
title_full_unstemmed Synthesis of Novel Benzenesulfonamide-Bearing Functionalized Imidazole Derivatives as Novel Candidates Targeting Multidrug-Resistant Mycobacterium abscessus Complex
title_short Synthesis of Novel Benzenesulfonamide-Bearing Functionalized Imidazole Derivatives as Novel Candidates Targeting Multidrug-Resistant Mycobacterium abscessus Complex
title_sort synthesis of novel benzenesulfonamide-bearing functionalized imidazole derivatives as novel candidates targeting multidrug-resistant mycobacterium abscessus complex
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10145568/
https://www.ncbi.nlm.nih.gov/pubmed/37110358
http://dx.doi.org/10.3390/microorganisms11040935
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