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Observation of Cytotoxicity of Phosphonium Derivatives Is Explained: Metabolism Inhibition and Adhesion Alteration

The search for new antibiotics, substances that kill prokaryotic cells and do not kill eukaryotic cells, is an urgent need for modern medicine. Among the most promising are derivatives of triphenylphosphonium, which can protect the infected organs of mammals and heal damaged cells as mitochondria-ta...

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Autores principales: Nazarov, Pavel A., Khrulnova, Svetlana A., Kessenikh, Andrew G., Novoyatlova, Uliana S., Kuznetsova, Svetlana B., Bazhenov, Sergey V., Sorochkina, Alexandra I., Karakozova, Marina V., Manukhov, Ilya V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10135132/
https://www.ncbi.nlm.nih.gov/pubmed/37107081
http://dx.doi.org/10.3390/antibiotics12040720
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author Nazarov, Pavel A.
Khrulnova, Svetlana A.
Kessenikh, Andrew G.
Novoyatlova, Uliana S.
Kuznetsova, Svetlana B.
Bazhenov, Sergey V.
Sorochkina, Alexandra I.
Karakozova, Marina V.
Manukhov, Ilya V.
author_facet Nazarov, Pavel A.
Khrulnova, Svetlana A.
Kessenikh, Andrew G.
Novoyatlova, Uliana S.
Kuznetsova, Svetlana B.
Bazhenov, Sergey V.
Sorochkina, Alexandra I.
Karakozova, Marina V.
Manukhov, Ilya V.
author_sort Nazarov, Pavel A.
collection PubMed
description The search for new antibiotics, substances that kill prokaryotic cells and do not kill eukaryotic cells, is an urgent need for modern medicine. Among the most promising are derivatives of triphenylphosphonium, which can protect the infected organs of mammals and heal damaged cells as mitochondria-targeted antioxidants. In addition to the antioxidant action, triphenylphosphonium derivatives exhibit antibacterial activity. It has recently been reported that triphenylphosphonium derivatives cause either cytotoxic effects or inhibition of cellular metabolism at submicromolar concentrations. In this work, we analyzed the MTT data using microscopy and compared them with data on changes in the luminescence of bacteria. We have shown that, at submicromolar concentrations, only metabolism is inhibited, while an increase in alkyltriphenylphosphonium (CnTPP) concentration leads to adhesion alteration. Thus, our data on eukaryotic and prokaryotic cells confirm a decrease in the metabolic activity of cells by CnTPPs but do not confirm a cytocidal effect of TPPs at submicromolar concentrations. This allows us to consider CnTPP as a non-toxic antibacterial drug at low concentrations and a relatively safe vector for delivering other antibacterial substances into bacterial cells.
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spelling pubmed-101351322023-04-28 Observation of Cytotoxicity of Phosphonium Derivatives Is Explained: Metabolism Inhibition and Adhesion Alteration Nazarov, Pavel A. Khrulnova, Svetlana A. Kessenikh, Andrew G. Novoyatlova, Uliana S. Kuznetsova, Svetlana B. Bazhenov, Sergey V. Sorochkina, Alexandra I. Karakozova, Marina V. Manukhov, Ilya V. Antibiotics (Basel) Article The search for new antibiotics, substances that kill prokaryotic cells and do not kill eukaryotic cells, is an urgent need for modern medicine. Among the most promising are derivatives of triphenylphosphonium, which can protect the infected organs of mammals and heal damaged cells as mitochondria-targeted antioxidants. In addition to the antioxidant action, triphenylphosphonium derivatives exhibit antibacterial activity. It has recently been reported that triphenylphosphonium derivatives cause either cytotoxic effects or inhibition of cellular metabolism at submicromolar concentrations. In this work, we analyzed the MTT data using microscopy and compared them with data on changes in the luminescence of bacteria. We have shown that, at submicromolar concentrations, only metabolism is inhibited, while an increase in alkyltriphenylphosphonium (CnTPP) concentration leads to adhesion alteration. Thus, our data on eukaryotic and prokaryotic cells confirm a decrease in the metabolic activity of cells by CnTPPs but do not confirm a cytocidal effect of TPPs at submicromolar concentrations. This allows us to consider CnTPP as a non-toxic antibacterial drug at low concentrations and a relatively safe vector for delivering other antibacterial substances into bacterial cells. MDPI 2023-04-06 /pmc/articles/PMC10135132/ /pubmed/37107081 http://dx.doi.org/10.3390/antibiotics12040720 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
Nazarov, Pavel A.
Khrulnova, Svetlana A.
Kessenikh, Andrew G.
Novoyatlova, Uliana S.
Kuznetsova, Svetlana B.
Bazhenov, Sergey V.
Sorochkina, Alexandra I.
Karakozova, Marina V.
Manukhov, Ilya V.
Observation of Cytotoxicity of Phosphonium Derivatives Is Explained: Metabolism Inhibition and Adhesion Alteration
title Observation of Cytotoxicity of Phosphonium Derivatives Is Explained: Metabolism Inhibition and Adhesion Alteration
title_full Observation of Cytotoxicity of Phosphonium Derivatives Is Explained: Metabolism Inhibition and Adhesion Alteration
title_fullStr Observation of Cytotoxicity of Phosphonium Derivatives Is Explained: Metabolism Inhibition and Adhesion Alteration
title_full_unstemmed Observation of Cytotoxicity of Phosphonium Derivatives Is Explained: Metabolism Inhibition and Adhesion Alteration
title_short Observation of Cytotoxicity of Phosphonium Derivatives Is Explained: Metabolism Inhibition and Adhesion Alteration
title_sort observation of cytotoxicity of phosphonium derivatives is explained: metabolism inhibition and adhesion alteration
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10135132/
https://www.ncbi.nlm.nih.gov/pubmed/37107081
http://dx.doi.org/10.3390/antibiotics12040720
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