Synthesis, Selected Transformations, and Biological Activity of Alkoxy Analogues of Lepidilines A and C
Condensation of diacetyl monooxime with formaldimines derived from alkoxyamines in glacial acetic acid at room temperature leads to corresponding 2-unsubstituted imidazole <i>N</i>-oxides bearing an alkoxy substituent at the N(1) atom of the imidazole ring. Subsequent <i>O</i>...
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| author | Grzegorz Mlostoń Małgorzata Celeda Wiktor Poper Mateusz Kowalczyk Katarzyna Gach-Janczak Anna Janecka Marcin Jasiński |
| author_facet | Grzegorz Mlostoń Małgorzata Celeda Wiktor Poper Mateusz Kowalczyk Katarzyna Gach-Janczak Anna Janecka Marcin Jasiński |
| author_sort | Grzegorz Mlostoń |
| collection | DOAJ |
| description | Condensation of diacetyl monooxime with formaldimines derived from alkoxyamines in glacial acetic acid at room temperature leads to corresponding 2-unsubstituted imidazole <i>N</i>-oxides bearing an alkoxy substituent at the N(1) atom of the imidazole ring. Subsequent <i>O</i>-benzylation afforded, depending on the type of alkylating agent, either symmetric or nonsymmetric alkoxyimidazolium salts considered as structural analogues of naturally occurring imidazole alkaloids, lepidilines A and C. Some of the obtained salts were tested as precursors of nucleophilic heterocyclic carbenes (NHCs), which in situ reacted with elemental sulfur to give the corresponding <i>N</i>-alkoxyimidazole-2-thiones. The cytotoxic activity of selected 4,5-dimethylimidazolium salts bearing either two benzyloxy or benzyloxy and 1-adamantyloxy groups at N(1) and N(3) atoms was evaluated against HL-60 and MCF-7 cell lines using the MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) assay. Notably, in two cases of alkoxyimidazolium salts, no effect of the counterion exchange (Br<sup>−</sup> → PF<sub>6</sub><sup>−</sup>) on the biological activity was observed. |
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| issn | 1996-1944 |
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| spelling | doaj.art-aecdeddae05c4f8faacc9c5521bf7ce12023-11-20T14:30:44ZengMDPI AGMaterials1996-19442020-09-011318419010.3390/ma13184190Synthesis, Selected Transformations, and Biological Activity of Alkoxy Analogues of Lepidilines A and CGrzegorz Mlostoń0Małgorzata Celeda1Wiktor Poper2Mateusz Kowalczyk3Katarzyna Gach-Janczak4Anna Janecka5Marcin Jasiński6Department of Organic and Applied Chemistry, Faculty of Chemistry, University of Łódź, Tamka 12, 91403 Łódź, PolandDepartment of Organic and Applied Chemistry, Faculty of Chemistry, University of Łódź, Tamka 12, 91403 Łódź, PolandDepartment of Organic and Applied Chemistry, Faculty of Chemistry, University of Łódź, Tamka 12, 91403 Łódź, PolandDepartment of Organic and Applied Chemistry, Faculty of Chemistry, University of Łódź, Tamka 12, 91403 Łódź, PolandDepartment of Biomolecular Chemistry, Medical University of Łódź, Mazowiecka 6/8, 92215 Łódź, PolandDepartment of Biomolecular Chemistry, Medical University of Łódź, Mazowiecka 6/8, 92215 Łódź, PolandDepartment of Organic and Applied Chemistry, Faculty of Chemistry, University of Łódź, Tamka 12, 91403 Łódź, PolandCondensation of diacetyl monooxime with formaldimines derived from alkoxyamines in glacial acetic acid at room temperature leads to corresponding 2-unsubstituted imidazole <i>N</i>-oxides bearing an alkoxy substituent at the N(1) atom of the imidazole ring. Subsequent <i>O</i>-benzylation afforded, depending on the type of alkylating agent, either symmetric or nonsymmetric alkoxyimidazolium salts considered as structural analogues of naturally occurring imidazole alkaloids, lepidilines A and C. Some of the obtained salts were tested as precursors of nucleophilic heterocyclic carbenes (NHCs), which in situ reacted with elemental sulfur to give the corresponding <i>N</i>-alkoxyimidazole-2-thiones. The cytotoxic activity of selected 4,5-dimethylimidazolium salts bearing either two benzyloxy or benzyloxy and 1-adamantyloxy groups at N(1) and N(3) atoms was evaluated against HL-60 and MCF-7 cell lines using the MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) assay. Notably, in two cases of alkoxyimidazolium salts, no effect of the counterion exchange (Br<sup>−</sup> → PF<sub>6</sub><sup>−</sup>) on the biological activity was observed.https://www.mdpi.com/1996-1944/13/18/4190imidazolium saltslepidiline alkaloidsimidazole <i>N</i>-oxides<i>N</i>-heterocyclic carbenessulfur-transfer reactionanticancer activity |
| spellingShingle | Grzegorz Mlostoń Małgorzata Celeda Wiktor Poper Mateusz Kowalczyk Katarzyna Gach-Janczak Anna Janecka Marcin Jasiński Synthesis, Selected Transformations, and Biological Activity of Alkoxy Analogues of Lepidilines A and C Materials imidazolium salts lepidiline alkaloids imidazole <i>N</i>-oxides <i>N</i>-heterocyclic carbenes sulfur-transfer reaction anticancer activity |
| title | Synthesis, Selected Transformations, and Biological Activity of Alkoxy Analogues of Lepidilines A and C |
| title_full | Synthesis, Selected Transformations, and Biological Activity of Alkoxy Analogues of Lepidilines A and C |
| title_fullStr | Synthesis, Selected Transformations, and Biological Activity of Alkoxy Analogues of Lepidilines A and C |
| title_full_unstemmed | Synthesis, Selected Transformations, and Biological Activity of Alkoxy Analogues of Lepidilines A and C |
| title_short | Synthesis, Selected Transformations, and Biological Activity of Alkoxy Analogues of Lepidilines A and C |
| title_sort | synthesis selected transformations and biological activity of alkoxy analogues of lepidilines a and c |
| topic | imidazolium salts lepidiline alkaloids imidazole <i>N</i>-oxides <i>N</i>-heterocyclic carbenes sulfur-transfer reaction anticancer activity |
| url | https://www.mdpi.com/1996-1944/13/18/4190 |
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