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Arylamine Analogs of Methylene Blue: Substituent Effect on Aggregation Behavior and DNA Binding
The synthesis of new phenothiazine derivatives, analogs of Methylene Blue, is of particular interest in the design of new drugs, as well as in the development of a new generation of agents for photodynamic therapy. In this study, two new derivatives of phenothiazine, i.e., 3,7-bis(4-aminophenylamino...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8198855/ https://www.ncbi.nlm.nih.gov/pubmed/34072560 http://dx.doi.org/10.3390/ijms22115847 |
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author | Khadieva, Alena Mostovaya, Olga Padnya, Pavel Kalinin, Valeriy Grishaev, Denis Tumakov, Dmitrii Stoikov, Ivan |
author_facet | Khadieva, Alena Mostovaya, Olga Padnya, Pavel Kalinin, Valeriy Grishaev, Denis Tumakov, Dmitrii Stoikov, Ivan |
author_sort | Khadieva, Alena |
collection | PubMed |
description | The synthesis of new phenothiazine derivatives, analogs of Methylene Blue, is of particular interest in the design of new drugs, as well as in the development of a new generation of agents for photodynamic therapy. In this study, two new derivatives of phenothiazine, i.e., 3,7-bis(4-aminophenylamino)phenothiazin-5-ium chloride dihydrochloride (PTZ1) and 3,7-bis(4-sulfophenylamino)phenothiazin-5-ium chloride (PTZ2), are synthesized for the first time and characterized by NMR, IR spectroscopy, HRMS and elemental analysis. The interaction of the obtained compounds PTZ1 and PTZ2 with salmon sperm DNA is investigated. It is shown by UV-Vis spectroscopy and DFT calculations that substituents in arylamine fragments play a crucial role in dimer formation and interaction with DNA. In the case of PTZ1, two amine groups promote H-aggregate formation and DNA interactions through groove binding and intercalation. In the case of PTZ2, sulfanilic acid fragments prevent any dimer formation and DNA binding due to electrostatic repulsion. DNA interaction mechanisms are studied and confirmed by UV-vis and fluorescence spectroscopy in comparison with Methylene Blue. The obtained results open significant opportunities for the development of new drugs and photodynamic agents. |
format | Online Article Text |
id | pubmed-8198855 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-81988552021-06-14 Arylamine Analogs of Methylene Blue: Substituent Effect on Aggregation Behavior and DNA Binding Khadieva, Alena Mostovaya, Olga Padnya, Pavel Kalinin, Valeriy Grishaev, Denis Tumakov, Dmitrii Stoikov, Ivan Int J Mol Sci Article The synthesis of new phenothiazine derivatives, analogs of Methylene Blue, is of particular interest in the design of new drugs, as well as in the development of a new generation of agents for photodynamic therapy. In this study, two new derivatives of phenothiazine, i.e., 3,7-bis(4-aminophenylamino)phenothiazin-5-ium chloride dihydrochloride (PTZ1) and 3,7-bis(4-sulfophenylamino)phenothiazin-5-ium chloride (PTZ2), are synthesized for the first time and characterized by NMR, IR spectroscopy, HRMS and elemental analysis. The interaction of the obtained compounds PTZ1 and PTZ2 with salmon sperm DNA is investigated. It is shown by UV-Vis spectroscopy and DFT calculations that substituents in arylamine fragments play a crucial role in dimer formation and interaction with DNA. In the case of PTZ1, two amine groups promote H-aggregate formation and DNA interactions through groove binding and intercalation. In the case of PTZ2, sulfanilic acid fragments prevent any dimer formation and DNA binding due to electrostatic repulsion. DNA interaction mechanisms are studied and confirmed by UV-vis and fluorescence spectroscopy in comparison with Methylene Blue. The obtained results open significant opportunities for the development of new drugs and photodynamic agents. MDPI 2021-05-29 /pmc/articles/PMC8198855/ /pubmed/34072560 http://dx.doi.org/10.3390/ijms22115847 Text en © 2021 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 Khadieva, Alena Mostovaya, Olga Padnya, Pavel Kalinin, Valeriy Grishaev, Denis Tumakov, Dmitrii Stoikov, Ivan Arylamine Analogs of Methylene Blue: Substituent Effect on Aggregation Behavior and DNA Binding |
title | Arylamine Analogs of Methylene Blue: Substituent Effect on Aggregation Behavior and DNA Binding |
title_full | Arylamine Analogs of Methylene Blue: Substituent Effect on Aggregation Behavior and DNA Binding |
title_fullStr | Arylamine Analogs of Methylene Blue: Substituent Effect on Aggregation Behavior and DNA Binding |
title_full_unstemmed | Arylamine Analogs of Methylene Blue: Substituent Effect on Aggregation Behavior and DNA Binding |
title_short | Arylamine Analogs of Methylene Blue: Substituent Effect on Aggregation Behavior and DNA Binding |
title_sort | arylamine analogs of methylene blue: substituent effect on aggregation behavior and dna binding |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8198855/ https://www.ncbi.nlm.nih.gov/pubmed/34072560 http://dx.doi.org/10.3390/ijms22115847 |
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