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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...

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Autores principales: Tikhonov, Sergey, Morozova, Natalia, Plutinskaya, Anna, Plotnikova, Ekaterina, Pankratov, Andrey, Abramova, Olga, Diachkova, Ekaterina, Vasil’ev, Yuriy, Grin, Mikhail
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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.
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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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