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The impact of counterions in biological activity: case study of antibacterial alkylguanidino ureas

ABSTRACT: Trifluoroacetic acid (TFA), due to its strong acidity and low boiling point, is extensively used in protecting groups-based synthetic strategies. Indeed, synthetic compounds bearing basic functions, such as amines or guanidines (commonly found in peptido or peptidomimetic derivatives), dev...

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Autores principales: Ardino, Claudia, Sannio, Filomena, Pasero, Carolina, Botta, Lorenzo, Dreassi, Elena, Docquier, Jean-Denis, D’Agostino, Ilaria
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9421121/
https://www.ncbi.nlm.nih.gov/pubmed/36036302
http://dx.doi.org/10.1007/s11030-022-10505-6
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author Ardino, Claudia
Sannio, Filomena
Pasero, Carolina
Botta, Lorenzo
Dreassi, Elena
Docquier, Jean-Denis
D’Agostino, Ilaria
author_facet Ardino, Claudia
Sannio, Filomena
Pasero, Carolina
Botta, Lorenzo
Dreassi, Elena
Docquier, Jean-Denis
D’Agostino, Ilaria
author_sort Ardino, Claudia
collection PubMed
description ABSTRACT: Trifluoroacetic acid (TFA), due to its strong acidity and low boiling point, is extensively used in protecting groups-based synthetic strategies. Indeed, synthetic compounds bearing basic functions, such as amines or guanidines (commonly found in peptido or peptidomimetic derivatives), developed in the frame of drug discovery programmes, are often isolated as trifluoroacetate (TF-Acetate) salts and their biological activity is assessed as such in in vitro, ex vivo, or in vivo experiments. However, the presence of residual amounts of TFA was reported to potentially affect the accuracy and reproducibility of a broad range of cellular assays (e. g. antimicrobial susceptibility testing, and cytotoxicity assays) limiting the further development of these derivatives. Furthermore, the impact of the counterion on biological activity, including TF-Acetate, is still controversial. Herein, we present a focused case study aiming to evaluate the activity of an antibacterial AlkylGuanidino Urea (AGU) compound obtained as TF-Acetate (1a) and hydrochloride (1b) salt forms to highlight the role of counterions in affecting the biological activity. We also prepared and tested the corresponding free base (1c). The exchange of the counterions applied to polyguanidino compounds represents an unexplored and challenging field, which required significant efforts for the successful optimization of reliable methods of preparation, also reported in this work. In the end, the biological evaluation revealed a quite similar biological profile for the salt derivatives 1a and 1b and a lower potency was found for the free base 1c. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11030-022-10505-6.
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spelling pubmed-94211212022-08-30 The impact of counterions in biological activity: case study of antibacterial alkylguanidino ureas Ardino, Claudia Sannio, Filomena Pasero, Carolina Botta, Lorenzo Dreassi, Elena Docquier, Jean-Denis D’Agostino, Ilaria Mol Divers Short Communication ABSTRACT: Trifluoroacetic acid (TFA), due to its strong acidity and low boiling point, is extensively used in protecting groups-based synthetic strategies. Indeed, synthetic compounds bearing basic functions, such as amines or guanidines (commonly found in peptido or peptidomimetic derivatives), developed in the frame of drug discovery programmes, are often isolated as trifluoroacetate (TF-Acetate) salts and their biological activity is assessed as such in in vitro, ex vivo, or in vivo experiments. However, the presence of residual amounts of TFA was reported to potentially affect the accuracy and reproducibility of a broad range of cellular assays (e. g. antimicrobial susceptibility testing, and cytotoxicity assays) limiting the further development of these derivatives. Furthermore, the impact of the counterion on biological activity, including TF-Acetate, is still controversial. Herein, we present a focused case study aiming to evaluate the activity of an antibacterial AlkylGuanidino Urea (AGU) compound obtained as TF-Acetate (1a) and hydrochloride (1b) salt forms to highlight the role of counterions in affecting the biological activity. We also prepared and tested the corresponding free base (1c). The exchange of the counterions applied to polyguanidino compounds represents an unexplored and challenging field, which required significant efforts for the successful optimization of reliable methods of preparation, also reported in this work. In the end, the biological evaluation revealed a quite similar biological profile for the salt derivatives 1a and 1b and a lower potency was found for the free base 1c. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11030-022-10505-6. Springer International Publishing 2022-08-29 /pmc/articles/PMC9421121/ /pubmed/36036302 http://dx.doi.org/10.1007/s11030-022-10505-6 Text en © The Author(s), under exclusive licence to Springer Nature Switzerland AG 2022 This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
spellingShingle Short Communication
Ardino, Claudia
Sannio, Filomena
Pasero, Carolina
Botta, Lorenzo
Dreassi, Elena
Docquier, Jean-Denis
D’Agostino, Ilaria
The impact of counterions in biological activity: case study of antibacterial alkylguanidino ureas
title The impact of counterions in biological activity: case study of antibacterial alkylguanidino ureas
title_full The impact of counterions in biological activity: case study of antibacterial alkylguanidino ureas
title_fullStr The impact of counterions in biological activity: case study of antibacterial alkylguanidino ureas
title_full_unstemmed The impact of counterions in biological activity: case study of antibacterial alkylguanidino ureas
title_short The impact of counterions in biological activity: case study of antibacterial alkylguanidino ureas
title_sort impact of counterions in biological activity: case study of antibacterial alkylguanidino ureas
topic Short Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9421121/
https://www.ncbi.nlm.nih.gov/pubmed/36036302
http://dx.doi.org/10.1007/s11030-022-10505-6
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