| Autor: |
Mlostoń G; Faculty of Chemistry, University of Lodz, 91403 Łódź, Poland., Kowalczyk M; Faculty of Chemistry, University of Lodz, 91403 Łódź, Poland.; The Bio-Med-Chem Doctoral School of the University of Lodz and Lodz Institutes of the Polish Academy of Sciences, Faculty of Biology and Environmental Protection, University of Lodz, 90237 Łódź, Poland., Celeda M; Faculty of Chemistry, University of Lodz, 91403 Łódź, Poland., Gach-Janczak K; Department of Biomolecular Chemistry, Medical University of Lodz, 92215 Łódź, Poland., Janecka A; Department of Biomolecular Chemistry, Medical University of Lodz, 92215 Łódź, Poland., Jasiński M; Faculty of Chemistry, University of Lodz, 91403 Łódź, Poland. |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of natural products [J Nat Prod] 2021 Dec 24; Vol. 84 (12), pp. 3071-3079. Date of Electronic Publication: 2021 Nov 22. |
| DOI: |
10.1021/acs.jnatprod.1c00797 |
| Abstrakt: |
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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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