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N-Heterocyclic Carbenes and Their Metal Complexes Based on Histidine and Histamine Derivatives of Bacteriopurpurinimide for the Combined Chemo- and Photodynamic Therapy of Cancer
Photodynamic therapy (PDT) is currently regarded as a promising method for the treatment of oncological diseases. However, it involves a number of limitations related to the specific features of the method and the specific characteristics of photosensitizer molecules, including tumor hypoxia, small...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9779690/ https://www.ncbi.nlm.nih.gov/pubmed/36555417 http://dx.doi.org/10.3390/ijms232415776 |
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author | Tikhonov, Sergey Morozova, Natalia Plutinskaya, Anna Plotnikova, Ekaterina Pankratov, Andrey Abramova, Olga Diachkova, Ekaterina Vasil’ev, Yuriy Grin, Mikhail |
author_facet | Tikhonov, Sergey Morozova, Natalia Plutinskaya, Anna Plotnikova, Ekaterina Pankratov, Andrey Abramova, Olga Diachkova, Ekaterina Vasil’ev, Yuriy Grin, Mikhail |
author_sort | Tikhonov, Sergey |
collection | PubMed |
description | Photodynamic therapy (PDT) is currently regarded as a promising method for the treatment of oncological diseases. However, it involves a number of limitations related to the specific features of the method and the specific characteristics of photosensitizer molecules, including tumor hypoxia, small depth of light penetration into the tumor tissue, and low accumulation sensitivity. These drawbacks can be overcome by combining PDT with other treatment methods, for example, chemotherapy. In this work, we were the first to obtain agents that contain bacteriopurpurinimide as a photodynamic subunit and complexes of gold(I) that implement the chemotherapy effect. To bind the latter agents, N-heterocyclic carbenes (NHC) based on histidine and histamine were obtained. We considered alternative techniques for synthesizing the target conjugates and selected an optimal one that enabled the production of preparative amounts for biological assays. In vitro studies showed that all the compounds obtained exhibited high photoinduced activity. The C-donor Au(I) complexes exhibited the maximum specific activity at longer incubation times compared to the other derivatives, both under exposure to light and without irradiation. In in vivo studies, the presence of histamine in the NHC-derivative of dipropoxy-BPI (7b) had no significant effect on its antitumor action, whereas the Au(I) metal complex of histamine NHC-derivative with BPI (8b) resulted in enhanced antitumor activity and in an increased number of remissions after photodynamic treatment. |
format | Online Article Text |
id | pubmed-9779690 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-97796902022-12-23 N-Heterocyclic Carbenes and Their Metal Complexes Based on Histidine and Histamine Derivatives of Bacteriopurpurinimide for the Combined Chemo- and Photodynamic Therapy of Cancer Tikhonov, Sergey Morozova, Natalia Plutinskaya, Anna Plotnikova, Ekaterina Pankratov, Andrey Abramova, Olga Diachkova, Ekaterina Vasil’ev, Yuriy Grin, Mikhail Int J Mol Sci Article Photodynamic therapy (PDT) is currently regarded as a promising method for the treatment of oncological diseases. However, it involves a number of limitations related to the specific features of the method and the specific characteristics of photosensitizer molecules, including tumor hypoxia, small depth of light penetration into the tumor tissue, and low accumulation sensitivity. These drawbacks can be overcome by combining PDT with other treatment methods, for example, chemotherapy. In this work, we were the first to obtain agents that contain bacteriopurpurinimide as a photodynamic subunit and complexes of gold(I) that implement the chemotherapy effect. To bind the latter agents, N-heterocyclic carbenes (NHC) based on histidine and histamine were obtained. We considered alternative techniques for synthesizing the target conjugates and selected an optimal one that enabled the production of preparative amounts for biological assays. In vitro studies showed that all the compounds obtained exhibited high photoinduced activity. The C-donor Au(I) complexes exhibited the maximum specific activity at longer incubation times compared to the other derivatives, both under exposure to light and without irradiation. In in vivo studies, the presence of histamine in the NHC-derivative of dipropoxy-BPI (7b) had no significant effect on its antitumor action, whereas the Au(I) metal complex of histamine NHC-derivative with BPI (8b) resulted in enhanced antitumor activity and in an increased number of remissions after photodynamic treatment. MDPI 2022-12-12 /pmc/articles/PMC9779690/ /pubmed/36555417 http://dx.doi.org/10.3390/ijms232415776 Text en © 2022 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 Tikhonov, Sergey Morozova, Natalia Plutinskaya, Anna Plotnikova, Ekaterina Pankratov, Andrey Abramova, Olga Diachkova, Ekaterina Vasil’ev, Yuriy Grin, Mikhail N-Heterocyclic Carbenes and Their Metal Complexes Based on Histidine and Histamine Derivatives of Bacteriopurpurinimide for the Combined Chemo- and Photodynamic Therapy of Cancer |
title | N-Heterocyclic Carbenes and Their Metal Complexes Based on Histidine and Histamine Derivatives of Bacteriopurpurinimide for the Combined Chemo- and Photodynamic Therapy of Cancer |
title_full | N-Heterocyclic Carbenes and Their Metal Complexes Based on Histidine and Histamine Derivatives of Bacteriopurpurinimide for the Combined Chemo- and Photodynamic Therapy of Cancer |
title_fullStr | N-Heterocyclic Carbenes and Their Metal Complexes Based on Histidine and Histamine Derivatives of Bacteriopurpurinimide for the Combined Chemo- and Photodynamic Therapy of Cancer |
title_full_unstemmed | N-Heterocyclic Carbenes and Their Metal Complexes Based on Histidine and Histamine Derivatives of Bacteriopurpurinimide for the Combined Chemo- and Photodynamic Therapy of Cancer |
title_short | N-Heterocyclic Carbenes and Their Metal Complexes Based on Histidine and Histamine Derivatives of Bacteriopurpurinimide for the Combined Chemo- and Photodynamic Therapy of Cancer |
title_sort | n-heterocyclic carbenes and their metal complexes based on histidine and histamine derivatives of bacteriopurpurinimide for the combined chemo- and photodynamic therapy of cancer |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9779690/ https://www.ncbi.nlm.nih.gov/pubmed/36555417 http://dx.doi.org/10.3390/ijms232415776 |
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