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Emergent antibacterial activity of N-(thiazol-2-yl)benzenesulfonamides in conjunction with cell-penetrating octaarginine

Hybrid antimicrobials that combine the effect of two or more agents represent a promising antibacterial therapeutic strategy. In this work, we have synthesized N-(4-(4-(methylsulfonyl)phenyl)-5-phenylthiazol-2-yl)benzenesulfonamide derivatives that combine thiazole and sulfonamide, groups with known...

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Autores principales: Ratrey, Poonam, Das Mahapatra, Amarjyoti, Pandit, Shiny, Hadianawala, Murtuza, Majhi, Sasmita, Mishra, Abhijit, Datta, Bhaskar
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society of Chemistry 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9038147/
https://www.ncbi.nlm.nih.gov/pubmed/35478531
http://dx.doi.org/10.1039/d1ra03882f
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author Ratrey, Poonam
Das Mahapatra, Amarjyoti
Pandit, Shiny
Hadianawala, Murtuza
Majhi, Sasmita
Mishra, Abhijit
Datta, Bhaskar
author_facet Ratrey, Poonam
Das Mahapatra, Amarjyoti
Pandit, Shiny
Hadianawala, Murtuza
Majhi, Sasmita
Mishra, Abhijit
Datta, Bhaskar
author_sort Ratrey, Poonam
collection PubMed
description Hybrid antimicrobials that combine the effect of two or more agents represent a promising antibacterial therapeutic strategy. In this work, we have synthesized N-(4-(4-(methylsulfonyl)phenyl)-5-phenylthiazol-2-yl)benzenesulfonamide derivatives that combine thiazole and sulfonamide, groups with known antibacterial activity. These molecules are investigated for their antibacterial activity, in isolation and in complex with the cell-penetrating peptide octaarginine. Several of the synthesized compounds display potent antibacterial activity against both Gram-negative and Gram-positive bacteria. Compounds with 4-tert-butyl and 4-isopropyl substitutions exhibit attractive antibacterial activity against multiple strains. The isopropyl substituted derivative displays low MIC of 3.9 μg mL(−1) against S. aureus and A. xylosoxidans. The comparative antibacterial behaviour of drug–peptide complex, drug alone and peptide alone indicates a distinctive mode of action of the drug–peptide complex, that is not the simple sum total of its constituent components. Specificity of the drug–peptide complex is evident from comparison of antibacterial behaviour with a synthetic intermediate–peptide complex. The octaarginine–drug complex displays faster killing-kinetics towards bacterial cells, creates pores in the bacterial cell membranes and shows negligible haemolytic activity towards human RBCs. Our results demonstrate that mere attachment of a hydrophobic moiety to a cell penetrating peptide does not impart antibacterial activity to the resultant complex. Conversely, the work suggests distinctive modes of antibiotic activity of small molecules when used in conjunction with a cell penetrating peptide.
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spelling pubmed-90381472022-04-26 Emergent antibacterial activity of N-(thiazol-2-yl)benzenesulfonamides in conjunction with cell-penetrating octaarginine Ratrey, Poonam Das Mahapatra, Amarjyoti Pandit, Shiny Hadianawala, Murtuza Majhi, Sasmita Mishra, Abhijit Datta, Bhaskar RSC Adv Chemistry Hybrid antimicrobials that combine the effect of two or more agents represent a promising antibacterial therapeutic strategy. In this work, we have synthesized N-(4-(4-(methylsulfonyl)phenyl)-5-phenylthiazol-2-yl)benzenesulfonamide derivatives that combine thiazole and sulfonamide, groups with known antibacterial activity. These molecules are investigated for their antibacterial activity, in isolation and in complex with the cell-penetrating peptide octaarginine. Several of the synthesized compounds display potent antibacterial activity against both Gram-negative and Gram-positive bacteria. Compounds with 4-tert-butyl and 4-isopropyl substitutions exhibit attractive antibacterial activity against multiple strains. The isopropyl substituted derivative displays low MIC of 3.9 μg mL(−1) against S. aureus and A. xylosoxidans. The comparative antibacterial behaviour of drug–peptide complex, drug alone and peptide alone indicates a distinctive mode of action of the drug–peptide complex, that is not the simple sum total of its constituent components. Specificity of the drug–peptide complex is evident from comparison of antibacterial behaviour with a synthetic intermediate–peptide complex. The octaarginine–drug complex displays faster killing-kinetics towards bacterial cells, creates pores in the bacterial cell membranes and shows negligible haemolytic activity towards human RBCs. Our results demonstrate that mere attachment of a hydrophobic moiety to a cell penetrating peptide does not impart antibacterial activity to the resultant complex. Conversely, the work suggests distinctive modes of antibiotic activity of small molecules when used in conjunction with a cell penetrating peptide. The Royal Society of Chemistry 2021-08-25 /pmc/articles/PMC9038147/ /pubmed/35478531 http://dx.doi.org/10.1039/d1ra03882f Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by-nc/3.0/
spellingShingle Chemistry
Ratrey, Poonam
Das Mahapatra, Amarjyoti
Pandit, Shiny
Hadianawala, Murtuza
Majhi, Sasmita
Mishra, Abhijit
Datta, Bhaskar
Emergent antibacterial activity of N-(thiazol-2-yl)benzenesulfonamides in conjunction with cell-penetrating octaarginine
title Emergent antibacterial activity of N-(thiazol-2-yl)benzenesulfonamides in conjunction with cell-penetrating octaarginine
title_full Emergent antibacterial activity of N-(thiazol-2-yl)benzenesulfonamides in conjunction with cell-penetrating octaarginine
title_fullStr Emergent antibacterial activity of N-(thiazol-2-yl)benzenesulfonamides in conjunction with cell-penetrating octaarginine
title_full_unstemmed Emergent antibacterial activity of N-(thiazol-2-yl)benzenesulfonamides in conjunction with cell-penetrating octaarginine
title_short Emergent antibacterial activity of N-(thiazol-2-yl)benzenesulfonamides in conjunction with cell-penetrating octaarginine
title_sort emergent antibacterial activity of n-(thiazol-2-yl)benzenesulfonamides in conjunction with cell-penetrating octaarginine
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9038147/
https://www.ncbi.nlm.nih.gov/pubmed/35478531
http://dx.doi.org/10.1039/d1ra03882f
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