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The In Vitro Antitumour Activity of Novel, Mitochondrial-Interactive, Gold-Based Lipophilic Cations

In this study we compared the effects of two previously described antimitochondrial gold complexes, that is, [A] [Au(dppe)(2)]Cl and [B] [Au(d4pype)(2)]Cl with two novel lipophilic cations, that is, [C] [Au(dpmaaH(2))(dpmaaSnMe(2))]Cl and [D] [Au(dpmaaSnMe(2))(2)]Cl as antimitochondrial agents. The...

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Autores principales: Mahepal, Sherika, Bowen, Richard, Mamo, Messai Adenew, Layh, Marcus, Jansen van Rensburg, Constance Elizabeth
Formato: Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2288641/
https://www.ncbi.nlm.nih.gov/pubmed/18401445
http://dx.doi.org/10.1155/2008/864653
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author Mahepal, Sherika
Bowen, Richard
Mamo, Messai Adenew
Layh, Marcus
Jansen van Rensburg, Constance Elizabeth
author_facet Mahepal, Sherika
Bowen, Richard
Mamo, Messai Adenew
Layh, Marcus
Jansen van Rensburg, Constance Elizabeth
author_sort Mahepal, Sherika
collection PubMed
description In this study we compared the effects of two previously described antimitochondrial gold complexes, that is, [A] [Au(dppe)(2)]Cl and [B] [Au(d4pype)(2)]Cl with two novel lipophilic cations, that is, [C] [Au(dpmaaH(2))(dpmaaSnMe(2))]Cl and [D] [Au(dpmaaSnMe(2))(2)]Cl as antimitochondrial agents. The results of this study indicate that [C] and [D] have intermediate partition coefficients and exhibited a selective uptake by cells. They exhibited a higher selectivity for the various cell lines than [A] but were more cytotoxic than [B]. There is a significant correlation between the cytotoxic potential of [A], [B], [C], and [D] and their octanol/water partition coefficients in both MCF-7 (breast cancer) and MCF-12A (nonmalignant breast) cells, whereas their cytotoxic potential and ability to induce the release of cytochrome c correlated only in the case of the MCF-12A cells. Complexes [C] and [D] are promising new chemotherapeutic drugs. These compounds target the mitochondrial membranes of certain cancer cells exploiting the differences between the mitochondrial membrane potential of these cells and normal cells. Although the concentrations of these compounds necessary to eradicate cancer cells are very high, the results provide a basis for the synthesis of a new family of compounds with intermediate partition coefficients compared to [A] and [B] but with increased activity against cancer cells.
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spelling pubmed-22886412008-04-09 The In Vitro Antitumour Activity of Novel, Mitochondrial-Interactive, Gold-Based Lipophilic Cations Mahepal, Sherika Bowen, Richard Mamo, Messai Adenew Layh, Marcus Jansen van Rensburg, Constance Elizabeth Met Based Drugs Research Article In this study we compared the effects of two previously described antimitochondrial gold complexes, that is, [A] [Au(dppe)(2)]Cl and [B] [Au(d4pype)(2)]Cl with two novel lipophilic cations, that is, [C] [Au(dpmaaH(2))(dpmaaSnMe(2))]Cl and [D] [Au(dpmaaSnMe(2))(2)]Cl as antimitochondrial agents. The results of this study indicate that [C] and [D] have intermediate partition coefficients and exhibited a selective uptake by cells. They exhibited a higher selectivity for the various cell lines than [A] but were more cytotoxic than [B]. There is a significant correlation between the cytotoxic potential of [A], [B], [C], and [D] and their octanol/water partition coefficients in both MCF-7 (breast cancer) and MCF-12A (nonmalignant breast) cells, whereas their cytotoxic potential and ability to induce the release of cytochrome c correlated only in the case of the MCF-12A cells. Complexes [C] and [D] are promising new chemotherapeutic drugs. These compounds target the mitochondrial membranes of certain cancer cells exploiting the differences between the mitochondrial membrane potential of these cells and normal cells. Although the concentrations of these compounds necessary to eradicate cancer cells are very high, the results provide a basis for the synthesis of a new family of compounds with intermediate partition coefficients compared to [A] and [B] but with increased activity against cancer cells. Hindawi Publishing Corporation 2008 2008-03-27 /pmc/articles/PMC2288641/ /pubmed/18401445 http://dx.doi.org/10.1155/2008/864653 Text en Copyright © 2008 Sherika Mahepal et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Mahepal, Sherika
Bowen, Richard
Mamo, Messai Adenew
Layh, Marcus
Jansen van Rensburg, Constance Elizabeth
The In Vitro Antitumour Activity of Novel, Mitochondrial-Interactive, Gold-Based Lipophilic Cations
title The In Vitro Antitumour Activity of Novel, Mitochondrial-Interactive, Gold-Based Lipophilic Cations
title_full The In Vitro Antitumour Activity of Novel, Mitochondrial-Interactive, Gold-Based Lipophilic Cations
title_fullStr The In Vitro Antitumour Activity of Novel, Mitochondrial-Interactive, Gold-Based Lipophilic Cations
title_full_unstemmed The In Vitro Antitumour Activity of Novel, Mitochondrial-Interactive, Gold-Based Lipophilic Cations
title_short The In Vitro Antitumour Activity of Novel, Mitochondrial-Interactive, Gold-Based Lipophilic Cations
title_sort in vitro antitumour activity of novel, mitochondrial-interactive, gold-based lipophilic cations
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2288641/
https://www.ncbi.nlm.nih.gov/pubmed/18401445
http://dx.doi.org/10.1155/2008/864653
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