Skvortsov Dmitry A, Emashova Sophia K, Kalinina Marina A, Dontsova Olga A
Department of Chemistry, Lomonosov Moscow State University, Moscow, Russia.
Ufa Scientific Centre, Institute of Biochemistry and Genetics Russian Academy of Science (IBG RAS), Ufa, Russia.
Arch Pharm (Weinheim). 2021 Mar;354(3):e2000281. doi: 10.1002/ardp.202000281. Epub 2020 Nov 27.
Delocalized lipophilic cations (DLCs) are known as mitochondria-addressed molecules. Mitochondria targeting may provide opportunities for tumor detection. DLCs may have antioxidant or anticancer properties. In this study, we focused on the toxicity and localization of 2-[(E)-2-(5-fluoro-2-methyl-1H-indol-3-yl)ethenyl]-1,6-dimethylpyridin-1-ium iodide (62E2), which has recently been found as a novel cytotoxic fluorescent compound. The excitation maximum of 62E2 is 452 ± 10 nm and its emission maximum is 579 ± 10 nm. It is accumulated in the cells and stains mitochondria in nanomolar concentrations. 62E2 is cytotoxic and mitotoxic in low micromolar concentrations, and it demonstrates some selectivity of cytotoxicity against A549 cancer cells. The closest analog of 62E2 is F16, which is the fluorescent mitotoxic agent that has been described earlier as a potential anticancer agent. We hope that 62E2 described here is useful in expanding the diversity of cyanine fluorescent mitochondrial dyes and the analysis of their structure-activity relationships.
离域亲脂性阳离子（DLCs）被认为是线粒体靶向分子。线粒体靶向可能为肿瘤检测提供机会。DLCs可能具有抗氧化或抗癌特性。在本研究中，我们重点关注了2-[(E)-2-(5-氟-2-甲基-1H-吲哚-3-基)乙烯基]-1,6-二甲基吡啶-1-鎓碘化物（62E2）的毒性和定位，该化合物最近被发现是一种新型细胞毒性荧光化合物。62E2的最大激发波长为452±10nm，最大发射波长为579±10nm。它在细胞中积累，并以纳摩尔浓度对线粒体进行染色。62E2在低微摩尔浓度下具有细胞毒性和线粒体毒性，并且对A549癌细胞表现出一定的细胞毒性选择性。62E2最接近的类似物是F16，F16是一种荧光线粒体毒性剂，之前被描述为一种潜在的抗癌剂。我们希望这里描述的62E2有助于扩大花菁荧光线粒体染料的多样性及其构效关系分析。
