Mlostoń Grzegorz, Celeda Małgorzata, Poper Wiktor, Kowalczyk Mateusz, Gach-Janczak Katarzyna, Janecka Anna, Jasiński Marcin
Department of Organic and Applied Chemistry, Faculty of Chemistry, University of Łódź, Tamka 12, 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 Łódź, Banacha 12/16, 90237 Łódź, Poland.
Materials (Basel). 2020 Sep 21;13(18):4190. doi: 10.3390/ma13184190.
Condensation of diacetyl monooxime with formaldimines derived from alkoxyamines in glacial acetic acid at room temperature leads to corresponding 2-unsubstituted imidazole -oxides bearing an alkoxy substituent at the N(1) atom of the imidazole ring. Subsequent -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 -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 → PF) on the biological activity was observed.
在室温下，二乙酰单肟与由烷氧基胺衍生的甲醛亚胺在冰醋酸中缩合，生成相应的在咪唑环的N(1)原子上带有烷氧基取代基的2-未取代咪唑氧化物。随后的苄基化反应，根据烷基化剂的类型，得到对称或不对称的烷氧基咪唑鎓盐，它们被认为是天然存在的咪唑生物碱lepidilines A和C的结构类似物。所得到的一些盐被测试作为亲核杂环卡宾（NHCs）的前体，其原位与元素硫反应生成相应的烷氧基咪唑-2-硫酮。使用MTT（3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐）测定法，评估了在N(1)和N(3)原子上带有两个苄氧基或苄氧基和1-金刚烷氧基的选定4,5-二甲基咪唑鎓盐对HL-60和MCF-7细胞系的细胞毒性活性。值得注意的是，在两例烷氧基咪唑鎓盐中，未观察到抗衡离子交换（Br→PF）对生物活性的影响。
