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New hits as phase II enzymes inducers from a focused library with heteroatom–heteroatom and Michael-acceptor motives
The increased activity of phase-II-detoxification enzymes, such as quinone reductase (QR) and glutation S-transferase (GST), correlates with protection against chemically induced carcinogenesis. Herein we studied 11 different chemotypes, pyrazole, 1,2,4-oxadiazole, 1,2,5-oxadiazole, 1,2,3-thiadiazol...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Future Science Ltd
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5137958/ https://www.ncbi.nlm.nih.gov/pubmed/28031894 http://dx.doi.org/10.4155/fso.15.18 |
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author | Cabrera, Mauricio de Ovalle, Stefani Bollati-Fogolín, Mariela Nascimento, Fabiana Corbelini, Patrícia Janarelli, Fernanda Kawano, Daniel Eifler-Lima, Vera Lucia González, Mercedes Cerecetto, Hugo |
author_facet | Cabrera, Mauricio de Ovalle, Stefani Bollati-Fogolín, Mariela Nascimento, Fabiana Corbelini, Patrícia Janarelli, Fernanda Kawano, Daniel Eifler-Lima, Vera Lucia González, Mercedes Cerecetto, Hugo |
author_sort | Cabrera, Mauricio |
collection | PubMed |
description | The increased activity of phase-II-detoxification enzymes, such as quinone reductase (QR) and glutation S-transferase (GST), correlates with protection against chemically induced carcinogenesis. Herein we studied 11 different chemotypes, pyrazole, 1,2,4-oxadiazole, 1,2,5-oxadiazole, 1,2,3-thiadiazole, 1,2,4-thiazole, 1,3,4-oxathiazole, thienyl hydrazone, α,β-unsaturated-oxime, α,β-unsaturated-N-oxide, coumarin and α,β-unsaturated-carbonyl, as phase-II enzymes inducers in order to identify new pharmacophores with chemopreventive activity. Fifty-four compounds were analyzed on wild-type mouse-hepatoma Hepa-1c1c7 and on the aryl-hydrocarbon-nuclear-translocator (Arnt)-defective mutant BpRc1 cells. New monofunctional inducers of QR and GST were identified, the 1,2,5-oxadiazol-2-oxide (3), the 1,2,4-triazine-4-oxides (23) and (32) and the tetrahydropyrimidinones (28) and (49). It was confirmed that Nrf2 nuclear translocation is the operative molecular mechanism that allows compound (3) to exert protective effects via expression of downstream phase-II enzymes. |
format | Online Article Text |
id | pubmed-5137958 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Future Science Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-51379582016-12-28 New hits as phase II enzymes inducers from a focused library with heteroatom–heteroatom and Michael-acceptor motives Cabrera, Mauricio de Ovalle, Stefani Bollati-Fogolín, Mariela Nascimento, Fabiana Corbelini, Patrícia Janarelli, Fernanda Kawano, Daniel Eifler-Lima, Vera Lucia González, Mercedes Cerecetto, Hugo Future Sci OA Research Article The increased activity of phase-II-detoxification enzymes, such as quinone reductase (QR) and glutation S-transferase (GST), correlates with protection against chemically induced carcinogenesis. Herein we studied 11 different chemotypes, pyrazole, 1,2,4-oxadiazole, 1,2,5-oxadiazole, 1,2,3-thiadiazole, 1,2,4-thiazole, 1,3,4-oxathiazole, thienyl hydrazone, α,β-unsaturated-oxime, α,β-unsaturated-N-oxide, coumarin and α,β-unsaturated-carbonyl, as phase-II enzymes inducers in order to identify new pharmacophores with chemopreventive activity. Fifty-four compounds were analyzed on wild-type mouse-hepatoma Hepa-1c1c7 and on the aryl-hydrocarbon-nuclear-translocator (Arnt)-defective mutant BpRc1 cells. New monofunctional inducers of QR and GST were identified, the 1,2,5-oxadiazol-2-oxide (3), the 1,2,4-triazine-4-oxides (23) and (32) and the tetrahydropyrimidinones (28) and (49). It was confirmed that Nrf2 nuclear translocation is the operative molecular mechanism that allows compound (3) to exert protective effects via expression of downstream phase-II enzymes. Future Science Ltd 2015-11-01 /pmc/articles/PMC5137958/ /pubmed/28031894 http://dx.doi.org/10.4155/fso.15.18 Text en © Mauricio Cabrera et al. This work is licensed under a Creative Commons Attribution 4.0 License (http://creativecommons.org/licenses/by/4.0/) |
spellingShingle | Research Article Cabrera, Mauricio de Ovalle, Stefani Bollati-Fogolín, Mariela Nascimento, Fabiana Corbelini, Patrícia Janarelli, Fernanda Kawano, Daniel Eifler-Lima, Vera Lucia González, Mercedes Cerecetto, Hugo New hits as phase II enzymes inducers from a focused library with heteroatom–heteroatom and Michael-acceptor motives |
title | New hits as phase II enzymes inducers from a focused library with heteroatom–heteroatom and Michael-acceptor motives |
title_full | New hits as phase II enzymes inducers from a focused library with heteroatom–heteroatom and Michael-acceptor motives |
title_fullStr | New hits as phase II enzymes inducers from a focused library with heteroatom–heteroatom and Michael-acceptor motives |
title_full_unstemmed | New hits as phase II enzymes inducers from a focused library with heteroatom–heteroatom and Michael-acceptor motives |
title_short | New hits as phase II enzymes inducers from a focused library with heteroatom–heteroatom and Michael-acceptor motives |
title_sort | new hits as phase ii enzymes inducers from a focused library with heteroatom–heteroatom and michael-acceptor motives |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5137958/ https://www.ncbi.nlm.nih.gov/pubmed/28031894 http://dx.doi.org/10.4155/fso.15.18 |
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