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...
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MDPI AG
2021-05-01
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| Series: | International Journal of Molecular Sciences |
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| author | Alena Khadieva Olga Mostovaya Pavel Padnya Valeriy Kalinin Denis Grishaev Dmitrii Tumakov Ivan Stoikov |
| author_facet | Alena Khadieva Olga Mostovaya Pavel Padnya Valeriy Kalinin Denis Grishaev Dmitrii Tumakov Ivan Stoikov |
| author_sort | Alena Khadieva |
| collection | DOAJ |
| 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 (<b>PTZ1</b>) and 3,7-bis(4-sulfophenylamino)phenothiazin-5-ium chloride (<b>PTZ2</b>), are synthesized for the first time and characterized by NMR, IR spectroscopy, HRMS and elemental analysis. The interaction of the obtained compounds <b>PTZ1</b> and <b>PTZ2</b> 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 <b>PTZ1</b>, two amine groups promote H-aggregate formation and DNA interactions through groove binding and intercalation. In the case of <b>PTZ2</b>, 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. |
| first_indexed | 2024-03-10T10:53:24Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T10:53:24Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-295f27dedd624b8d86294a9fd3b563832023-11-21T22:02:29ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-05-012211584710.3390/ijms22115847Arylamine Analogs of Methylene Blue: Substituent Effect on Aggregation Behavior and DNA BindingAlena Khadieva0Olga Mostovaya1Pavel Padnya2Valeriy Kalinin3Denis Grishaev4Dmitrii Tumakov5Ivan Stoikov6A.M. Butlerov’ Chemistry Institute of Kazan Federal University, 18 Kremlyovskaya Str., 420008 Kazan, RussiaA.M. Butlerov’ Chemistry Institute of Kazan Federal University, 18 Kremlyovskaya Str., 420008 Kazan, RussiaA.M. Butlerov’ Chemistry Institute of Kazan Federal University, 18 Kremlyovskaya Str., 420008 Kazan, RussiaA.M. Butlerov’ Chemistry Institute of Kazan Federal University, 18 Kremlyovskaya Str., 420008 Kazan, RussiaScientific and Educational Center of Pharmaceutics, Kazan Federal University, 420008 Kazan, RussiaInstitute of Computational Mathematics and Information Technologies, Kazan Federal University, 420008 Kazan, RussiaA.M. Butlerov’ Chemistry Institute of Kazan Federal University, 18 Kremlyovskaya Str., 420008 Kazan, RussiaThe 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 (<b>PTZ1</b>) and 3,7-bis(4-sulfophenylamino)phenothiazin-5-ium chloride (<b>PTZ2</b>), are synthesized for the first time and characterized by NMR, IR spectroscopy, HRMS and elemental analysis. The interaction of the obtained compounds <b>PTZ1</b> and <b>PTZ2</b> 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 <b>PTZ1</b>, two amine groups promote H-aggregate formation and DNA interactions through groove binding and intercalation. In the case of <b>PTZ2</b>, 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.https://www.mdpi.com/1422-0067/22/11/5847methylene bluephenothiazine3,7-bis(N-phenylamino)phenothiazin-5-iumsDNAintercalationdimerization |
| spellingShingle | Alena Khadieva Olga Mostovaya Pavel Padnya Valeriy Kalinin Denis Grishaev Dmitrii Tumakov Ivan Stoikov Arylamine Analogs of Methylene Blue: Substituent Effect on Aggregation Behavior and DNA Binding International Journal of Molecular Sciences methylene blue phenothiazine 3,7-bis(N-phenylamino)phenothiazin-5-iums DNA intercalation dimerization |
| 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 | methylene blue phenothiazine 3,7-bis(N-phenylamino)phenothiazin-5-iums DNA intercalation dimerization |
| url | https://www.mdpi.com/1422-0067/22/11/5847 |
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