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Effects of Substitution on Cytotoxicity of Diphenyl Ditelluride in Cultured Vascular Endothelial Cells

Among organic–inorganic hybrid molecules consisting of organic structure(s) and metal(s), only few studies are available on the cytotoxicity of nucleophilic molecules. In the present study, we investigated the cytotoxicity of a nucleophilic organotellurium compound, diphenyl ditelluride (DPDTe), usi...

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Autores principales: Hara, Takato, Okazaki, Takahiro, Hashiya, Tamayo, Nozawa, Kyohei, Yasuike, Shuji, Kurita, Jyoji, Yamamoto, Chika, Hamada, Noriaki, Kaji, Toshiyuki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8531998/
https://www.ncbi.nlm.nih.gov/pubmed/34638861
http://dx.doi.org/10.3390/ijms221910520
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author Hara, Takato
Okazaki, Takahiro
Hashiya, Tamayo
Nozawa, Kyohei
Yasuike, Shuji
Kurita, Jyoji
Yamamoto, Chika
Hamada, Noriaki
Kaji, Toshiyuki
author_facet Hara, Takato
Okazaki, Takahiro
Hashiya, Tamayo
Nozawa, Kyohei
Yasuike, Shuji
Kurita, Jyoji
Yamamoto, Chika
Hamada, Noriaki
Kaji, Toshiyuki
author_sort Hara, Takato
collection PubMed
description Among organic–inorganic hybrid molecules consisting of organic structure(s) and metal(s), only few studies are available on the cytotoxicity of nucleophilic molecules. In the present study, we investigated the cytotoxicity of a nucleophilic organotellurium compound, diphenyl ditelluride (DPDTe), using a cell culture system. DPDTe exhibited strong cytotoxicity against vascular endothelial cells and fibroblasts along with high intracellular accumulation but showed no cytotoxicity and had less accumulation in vascular smooth muscle cells and renal epithelial cells. The cytotoxicity of DPDTe decreased when intramolecular tellurium atoms were replaced with selenium or sulfur atoms. Electronic state analysis revealed that the electron density between tellurium atoms in DPDTe was much lower than those between selenium atoms of diphenyl diselenide and sulfur atoms of diphenyl disulfide. Moreover, diphenyl telluride did not accumulate and exhibit cytotoxicity. The cytotoxicity of DPDTe was also affected by substitution. p-Dimethoxy-DPDTe showed higher cytotoxicity, but p-dichloro-DPDTe and p-methyl-DPDTe showed lower cytotoxicity than that of DPDTe. The subcellular distribution of the compounds revealed that the compounds with stronger cytotoxicity showed higher accumulation rates in the mitochondria. Our findings suggest that the electronic state of tellurium atoms in DPDTe play an important role in accumulation and distribution of DPDTe in cultured cells. The present study supports the hypothesis that nucleophilic organometallic compounds, as well as electrophilic organometallic compounds, exhibit cytotoxicity by particular mechanisms.
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spelling pubmed-85319982021-10-23 Effects of Substitution on Cytotoxicity of Diphenyl Ditelluride in Cultured Vascular Endothelial Cells Hara, Takato Okazaki, Takahiro Hashiya, Tamayo Nozawa, Kyohei Yasuike, Shuji Kurita, Jyoji Yamamoto, Chika Hamada, Noriaki Kaji, Toshiyuki Int J Mol Sci Article Among organic–inorganic hybrid molecules consisting of organic structure(s) and metal(s), only few studies are available on the cytotoxicity of nucleophilic molecules. In the present study, we investigated the cytotoxicity of a nucleophilic organotellurium compound, diphenyl ditelluride (DPDTe), using a cell culture system. DPDTe exhibited strong cytotoxicity against vascular endothelial cells and fibroblasts along with high intracellular accumulation but showed no cytotoxicity and had less accumulation in vascular smooth muscle cells and renal epithelial cells. The cytotoxicity of DPDTe decreased when intramolecular tellurium atoms were replaced with selenium or sulfur atoms. Electronic state analysis revealed that the electron density between tellurium atoms in DPDTe was much lower than those between selenium atoms of diphenyl diselenide and sulfur atoms of diphenyl disulfide. Moreover, diphenyl telluride did not accumulate and exhibit cytotoxicity. The cytotoxicity of DPDTe was also affected by substitution. p-Dimethoxy-DPDTe showed higher cytotoxicity, but p-dichloro-DPDTe and p-methyl-DPDTe showed lower cytotoxicity than that of DPDTe. The subcellular distribution of the compounds revealed that the compounds with stronger cytotoxicity showed higher accumulation rates in the mitochondria. Our findings suggest that the electronic state of tellurium atoms in DPDTe play an important role in accumulation and distribution of DPDTe in cultured cells. The present study supports the hypothesis that nucleophilic organometallic compounds, as well as electrophilic organometallic compounds, exhibit cytotoxicity by particular mechanisms. MDPI 2021-09-29 /pmc/articles/PMC8531998/ /pubmed/34638861 http://dx.doi.org/10.3390/ijms221910520 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
Hara, Takato
Okazaki, Takahiro
Hashiya, Tamayo
Nozawa, Kyohei
Yasuike, Shuji
Kurita, Jyoji
Yamamoto, Chika
Hamada, Noriaki
Kaji, Toshiyuki
Effects of Substitution on Cytotoxicity of Diphenyl Ditelluride in Cultured Vascular Endothelial Cells
title Effects of Substitution on Cytotoxicity of Diphenyl Ditelluride in Cultured Vascular Endothelial Cells
title_full Effects of Substitution on Cytotoxicity of Diphenyl Ditelluride in Cultured Vascular Endothelial Cells
title_fullStr Effects of Substitution on Cytotoxicity of Diphenyl Ditelluride in Cultured Vascular Endothelial Cells
title_full_unstemmed Effects of Substitution on Cytotoxicity of Diphenyl Ditelluride in Cultured Vascular Endothelial Cells
title_short Effects of Substitution on Cytotoxicity of Diphenyl Ditelluride in Cultured Vascular Endothelial Cells
title_sort effects of substitution on cytotoxicity of diphenyl ditelluride in cultured vascular endothelial cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8531998/
https://www.ncbi.nlm.nih.gov/pubmed/34638861
http://dx.doi.org/10.3390/ijms221910520
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