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1,2-dithiol-3-thione and dithioester analogues: potential radioprotectors.
Several 1,2-dithiol-3-thione and dithioester compounds were assayed for radioprotective capabilities in EMT6 cells in vitro. The 1,2-dithiol-3-thiones were generally more cytotoxic than the dithioesters and in some instances were more cytotoxic toward hypoxic cells than toward normally oxygenated ce...
Autores principales: | , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Nature Publishing Group
1990
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1971736/ https://www.ncbi.nlm.nih.gov/pubmed/2390477 |
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author | Teicher, B. A. Stemwedel, J. Herman, T. S. Ghoshal, P. K. Rosowsky, A. |
author_facet | Teicher, B. A. Stemwedel, J. Herman, T. S. Ghoshal, P. K. Rosowsky, A. |
author_sort | Teicher, B. A. |
collection | PubMed |
description | Several 1,2-dithiol-3-thione and dithioester compounds were assayed for radioprotective capabilities in EMT6 cells in vitro. The 1,2-dithiol-3-thiones were generally more cytotoxic than the dithioesters and in some instances were more cytotoxic toward hypoxic cells than toward normally oxygenated cells. When the drugs were present at a concentration of 500 microM for 1 h prior to and during radiation delivery, the 5-(2-thienyl)-1,2-dithiol-3-thione produced a radiation protection factor (RPF) of 2.7 at 1 log of cell kill. The 4-methyl analogue of this same compound was, however, much less effective, producing a RPF of only 1.2. The 4-ethoxycarbonyl analogue was moderately active, producing a RPF of 1.7. The 4-methyl-5-(2-pyrazinyl)-1,2-dithiol-3-thione (Oltipraz) was least effective, yielding a RPF of only 1.1. Of the dithioesters tested, methyl 3-pyrrolidino-2-phenylpropene dithiocarboxylate produced a RPF of 2.6, methyl 3-piperidino-2-phenylpropenedithiocarboxylate a RPF of 2.7, and the corresponding 3-morpholino and 3-thiomorpholino derivatives RPF values of 2.7 and 2.9, respectively. The iodide salt of 4-ethoxycarbonyl-5-(2-thienyl)-1,2-dithiol-3-thione produced a RPF of 2.6 Methyl 3-cyclohexylamino-2-phenylpropenedithiocarboxylate was equally effective (RPF = 2.6). Finally, methyl 3-morpholino-3-thienyl-2-methylpropenedithiocarboxylate and methyl 3-morpholino-3-(2-pyrazinyl)-2-methylpropenedithiocarboxylate were less effective, producing RPF values of 2.0 and 1.6, respectively. These results demonstrate that several of these compounds are highly effective radioprotectors. In vitro and in vivo studies testing their efficacy are underway. |
format | Text |
id | pubmed-1971736 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 1990 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-19717362009-09-10 1,2-dithiol-3-thione and dithioester analogues: potential radioprotectors. Teicher, B. A. Stemwedel, J. Herman, T. S. Ghoshal, P. K. Rosowsky, A. Br J Cancer Research Article Several 1,2-dithiol-3-thione and dithioester compounds were assayed for radioprotective capabilities in EMT6 cells in vitro. The 1,2-dithiol-3-thiones were generally more cytotoxic than the dithioesters and in some instances were more cytotoxic toward hypoxic cells than toward normally oxygenated cells. When the drugs were present at a concentration of 500 microM for 1 h prior to and during radiation delivery, the 5-(2-thienyl)-1,2-dithiol-3-thione produced a radiation protection factor (RPF) of 2.7 at 1 log of cell kill. The 4-methyl analogue of this same compound was, however, much less effective, producing a RPF of only 1.2. The 4-ethoxycarbonyl analogue was moderately active, producing a RPF of 1.7. The 4-methyl-5-(2-pyrazinyl)-1,2-dithiol-3-thione (Oltipraz) was least effective, yielding a RPF of only 1.1. Of the dithioesters tested, methyl 3-pyrrolidino-2-phenylpropene dithiocarboxylate produced a RPF of 2.6, methyl 3-piperidino-2-phenylpropenedithiocarboxylate a RPF of 2.7, and the corresponding 3-morpholino and 3-thiomorpholino derivatives RPF values of 2.7 and 2.9, respectively. The iodide salt of 4-ethoxycarbonyl-5-(2-thienyl)-1,2-dithiol-3-thione produced a RPF of 2.6 Methyl 3-cyclohexylamino-2-phenylpropenedithiocarboxylate was equally effective (RPF = 2.6). Finally, methyl 3-morpholino-3-thienyl-2-methylpropenedithiocarboxylate and methyl 3-morpholino-3-(2-pyrazinyl)-2-methylpropenedithiocarboxylate were less effective, producing RPF values of 2.0 and 1.6, respectively. These results demonstrate that several of these compounds are highly effective radioprotectors. In vitro and in vivo studies testing their efficacy are underway. Nature Publishing Group 1990-07 /pmc/articles/PMC1971736/ /pubmed/2390477 Text en https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Research Article Teicher, B. A. Stemwedel, J. Herman, T. S. Ghoshal, P. K. Rosowsky, A. 1,2-dithiol-3-thione and dithioester analogues: potential radioprotectors. |
title | 1,2-dithiol-3-thione and dithioester analogues: potential radioprotectors. |
title_full | 1,2-dithiol-3-thione and dithioester analogues: potential radioprotectors. |
title_fullStr | 1,2-dithiol-3-thione and dithioester analogues: potential radioprotectors. |
title_full_unstemmed | 1,2-dithiol-3-thione and dithioester analogues: potential radioprotectors. |
title_short | 1,2-dithiol-3-thione and dithioester analogues: potential radioprotectors. |
title_sort | 1,2-dithiol-3-thione and dithioester analogues: potential radioprotectors. |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1971736/ https://www.ncbi.nlm.nih.gov/pubmed/2390477 |
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