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Synthesis and Antibacterial Activity of Cationic Amino Acid-Conjugated Dendrimers Loaded with a Mixture of Two Triterpenoid Acids

To counteract the growing bacterial resistance, we previously reported the remarkable antimicrobial activity of amino acid-conjugated cationic dendrimers (CDs) against several Gram-negative species, establishing that the cationic lysine was essential for their potency. In this paper, CDs conjugated...

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Autores principales: Schito, Anna Maria, Schito, Gian Carlo, Alfei, Silvana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7916190/
https://www.ncbi.nlm.nih.gov/pubmed/33572439
http://dx.doi.org/10.3390/polym13040521
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author Schito, Anna Maria
Schito, Gian Carlo
Alfei, Silvana
author_facet Schito, Anna Maria
Schito, Gian Carlo
Alfei, Silvana
author_sort Schito, Anna Maria
collection PubMed
description To counteract the growing bacterial resistance, we previously reported the remarkable antimicrobial activity of amino acid-conjugated cationic dendrimers (CDs) against several Gram-negative species, establishing that the cationic lysine was essential for their potency. In this paper, CDs conjugated with lysine and arginine and encapsulating ursolic and oleanolic acids (UOACDs) were assumed to be excellent candidates for developing new antibacterial agents, possibly active against Gram-positive species. Indeed, both the guanidine group of arginine and the two triterpenoid acids are items known for directing antibacterial effects, particularly against Gram-positive bacteria. The cationic dendrimers were obtained by peripheral conjugation with the selected amino acids and by entrapping a physical mixture of the commercial triterpenoid acids. The cationic compounds were characterized and successfully tested against 15 Gram-positive isolates. Interesting minimum inhibitory concentration (MIC) values were obtained for all the dendrimer-drug agents, establishing that the antibacterial activity observed for the UOACDs strongly depended on the density and on the type of the cationic groups of the cationic amino acid-conjugated dendrimers and not on the presence and the release of UOA. Particularly, lysine was critical for potency, while arginine was critical for redirecting activity against Gram-positive species. Especially, a high cationic character, associated with a balanced content of lysine/arginine, produced a remarkable antimicrobial effect (MIC = 0.5–8.7 µM).
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spelling pubmed-79161902021-03-01 Synthesis and Antibacterial Activity of Cationic Amino Acid-Conjugated Dendrimers Loaded with a Mixture of Two Triterpenoid Acids Schito, Anna Maria Schito, Gian Carlo Alfei, Silvana Polymers (Basel) Article To counteract the growing bacterial resistance, we previously reported the remarkable antimicrobial activity of amino acid-conjugated cationic dendrimers (CDs) against several Gram-negative species, establishing that the cationic lysine was essential for their potency. In this paper, CDs conjugated with lysine and arginine and encapsulating ursolic and oleanolic acids (UOACDs) were assumed to be excellent candidates for developing new antibacterial agents, possibly active against Gram-positive species. Indeed, both the guanidine group of arginine and the two triterpenoid acids are items known for directing antibacterial effects, particularly against Gram-positive bacteria. The cationic dendrimers were obtained by peripheral conjugation with the selected amino acids and by entrapping a physical mixture of the commercial triterpenoid acids. The cationic compounds were characterized and successfully tested against 15 Gram-positive isolates. Interesting minimum inhibitory concentration (MIC) values were obtained for all the dendrimer-drug agents, establishing that the antibacterial activity observed for the UOACDs strongly depended on the density and on the type of the cationic groups of the cationic amino acid-conjugated dendrimers and not on the presence and the release of UOA. Particularly, lysine was critical for potency, while arginine was critical for redirecting activity against Gram-positive species. Especially, a high cationic character, associated with a balanced content of lysine/arginine, produced a remarkable antimicrobial effect (MIC = 0.5–8.7 µM). MDPI 2021-02-09 /pmc/articles/PMC7916190/ /pubmed/33572439 http://dx.doi.org/10.3390/polym13040521 Text en © 2021 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Schito, Anna Maria
Schito, Gian Carlo
Alfei, Silvana
Synthesis and Antibacterial Activity of Cationic Amino Acid-Conjugated Dendrimers Loaded with a Mixture of Two Triterpenoid Acids
title Synthesis and Antibacterial Activity of Cationic Amino Acid-Conjugated Dendrimers Loaded with a Mixture of Two Triterpenoid Acids
title_full Synthesis and Antibacterial Activity of Cationic Amino Acid-Conjugated Dendrimers Loaded with a Mixture of Two Triterpenoid Acids
title_fullStr Synthesis and Antibacterial Activity of Cationic Amino Acid-Conjugated Dendrimers Loaded with a Mixture of Two Triterpenoid Acids
title_full_unstemmed Synthesis and Antibacterial Activity of Cationic Amino Acid-Conjugated Dendrimers Loaded with a Mixture of Two Triterpenoid Acids
title_short Synthesis and Antibacterial Activity of Cationic Amino Acid-Conjugated Dendrimers Loaded with a Mixture of Two Triterpenoid Acids
title_sort synthesis and antibacterial activity of cationic amino acid-conjugated dendrimers loaded with a mixture of two triterpenoid acids
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7916190/
https://www.ncbi.nlm.nih.gov/pubmed/33572439
http://dx.doi.org/10.3390/polym13040521
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