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Synthesis and Cytotoxic Activity of Lepidilines A–D: Comparison with Some 4,5-Diphenyl Analogues and Related Imidazole-2-thiones
[Image: see text] A straightforward access to 2-unsubstituted imidazole N-oxides with subsequent deoxygenation by treatment with Raney-nickel followed by N-benzylation opens up a convenient route to lepidilines A and C. Both imidazolium salts were used to generate in situ the corresponding imidazol-...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical Society and American Society of Pharmacognosy
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8713287/ https://www.ncbi.nlm.nih.gov/pubmed/34808062 http://dx.doi.org/10.1021/acs.jnatprod.1c00797 |
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author | Mlostoń, Grzegorz Kowalczyk, Mateusz Celeda, Małgorzata Gach-Janczak, Katarzyna Janecka, Anna Jasiński, Marcin |
author_facet | Mlostoń, Grzegorz Kowalczyk, Mateusz Celeda, Małgorzata Gach-Janczak, Katarzyna Janecka, Anna Jasiński, Marcin |
author_sort | Mlostoń, Grzegorz |
collection | PubMed |
description | [Image: see text] A straightforward access to 2-unsubstituted imidazole N-oxides with subsequent deoxygenation by treatment with Raney-nickel followed by N-benzylation opens up a convenient route to lepidilines A and C. Both imidazolium salts were used to generate in situ the corresponding imidazol-2-ylidenes, which smoothly reacted with elemental sulfur, yielding imidazole-2-thiones. These reactions were performed either under classical conditions in pyridine solutions or mechanochemically using solid Cs(2)CO(3) as a base. The structure of lepidiline C was unambiguously confirmed by X-ray analysis of its hexafluorophosphate. An analogous protocol toward lepidilines B and D and their 4,5-diphenyl analogues is less efficient due to observed instability of the key precursors, i.e., the respective 2-methylimidazole N-oxides. Comparison of cytotoxic activity against HL-60 and MCF-7 cell lines of all lepidilines, as well as their selected structural analogues (e.g., 4,5-diphenyl derivatives and PF(6) salts), revealed slightly more potent activity of the 2-methylated series, irrespectively of the type of counterion present in the imidazolium salt. Remarkably, the well-known 1,3-diadamantylimidazolium bromide (the “Arduengo salt”), known as the precursor of the first, shelf-stable NHC representative, and its adamantyloxy analogue displayed the most significant cytotoxic activity in the studied series. |
format | Online Article Text |
id | pubmed-8713287 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Chemical Society and American Society of Pharmacognosy |
record_format | MEDLINE/PubMed |
spelling | pubmed-87132872021-12-28 Synthesis and Cytotoxic Activity of Lepidilines A–D: Comparison with Some 4,5-Diphenyl Analogues and Related Imidazole-2-thiones Mlostoń, Grzegorz Kowalczyk, Mateusz Celeda, Małgorzata Gach-Janczak, Katarzyna Janecka, Anna Jasiński, Marcin J Nat Prod [Image: see text] A straightforward access to 2-unsubstituted imidazole N-oxides with subsequent deoxygenation by treatment with Raney-nickel followed by N-benzylation opens up a convenient route to lepidilines A and C. Both imidazolium salts were used to generate in situ the corresponding imidazol-2-ylidenes, which smoothly reacted with elemental sulfur, yielding imidazole-2-thiones. These reactions were performed either under classical conditions in pyridine solutions or mechanochemically using solid Cs(2)CO(3) as a base. The structure of lepidiline C was unambiguously confirmed by X-ray analysis of its hexafluorophosphate. An analogous protocol toward lepidilines B and D and their 4,5-diphenyl analogues is less efficient due to observed instability of the key precursors, i.e., the respective 2-methylimidazole N-oxides. Comparison of cytotoxic activity against HL-60 and MCF-7 cell lines of all lepidilines, as well as their selected structural analogues (e.g., 4,5-diphenyl derivatives and PF(6) salts), revealed slightly more potent activity of the 2-methylated series, irrespectively of the type of counterion present in the imidazolium salt. Remarkably, the well-known 1,3-diadamantylimidazolium bromide (the “Arduengo salt”), known as the precursor of the first, shelf-stable NHC representative, and its adamantyloxy analogue displayed the most significant cytotoxic activity in the studied series. American Chemical Society and American Society of Pharmacognosy 2021-11-22 2021-12-24 /pmc/articles/PMC8713287/ /pubmed/34808062 http://dx.doi.org/10.1021/acs.jnatprod.1c00797 Text en © 2021 The Authors. Published by American Chemical Society and American Society of Pharmacognosy https://creativecommons.org/licenses/by/4.0/Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Mlostoń, Grzegorz Kowalczyk, Mateusz Celeda, Małgorzata Gach-Janczak, Katarzyna Janecka, Anna Jasiński, Marcin Synthesis and Cytotoxic Activity of Lepidilines A–D: Comparison with Some 4,5-Diphenyl Analogues and Related Imidazole-2-thiones |
title | Synthesis and Cytotoxic Activity of Lepidilines A–D:
Comparison with Some 4,5-Diphenyl Analogues and Related Imidazole-2-thiones |
title_full | Synthesis and Cytotoxic Activity of Lepidilines A–D:
Comparison with Some 4,5-Diphenyl Analogues and Related Imidazole-2-thiones |
title_fullStr | Synthesis and Cytotoxic Activity of Lepidilines A–D:
Comparison with Some 4,5-Diphenyl Analogues and Related Imidazole-2-thiones |
title_full_unstemmed | Synthesis and Cytotoxic Activity of Lepidilines A–D:
Comparison with Some 4,5-Diphenyl Analogues and Related Imidazole-2-thiones |
title_short | Synthesis and Cytotoxic Activity of Lepidilines A–D:
Comparison with Some 4,5-Diphenyl Analogues and Related Imidazole-2-thiones |
title_sort | synthesis and cytotoxic activity of lepidilines a–d:
comparison with some 4,5-diphenyl analogues and related imidazole-2-thiones |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8713287/ https://www.ncbi.nlm.nih.gov/pubmed/34808062 http://dx.doi.org/10.1021/acs.jnatprod.1c00797 |
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