Synthesis of triphenylphosphonium dibenzothiophene S-oxide derivatives and their effect on cell cycle as photodeoxygenation-based cytotoxic agents
Synthesis of triphenylphosphonium dibenzothiophene S-oxide derivatives and their effect on cell cycle as photodeoxygenation-based cytotoxic agents
复制标题
三苯基鏻二苯并噻吩S-氧化物衍生物的合成及其作为光脱氧细胞毒剂对细胞周期的影响
DOI：
10.1016/j.bioorg.2020.104442
复制
发表时间：
2020
影响因子：
5.1
通讯作者：
McCulla, Ryan D.
中科院分区：
文献类型：
--
作者：
Isor, Ankita;O'Dea, Austin T.;Petroff, John T.;Skubic, Kristin N.;Grady, Scott F.;Arnatt, Christopher K.;McCulla, Ryan D.
二苯并硫-S氧化物在UV-A光下的光脱氧反应生成原子氧[O(3P)]和相应的硫化物--二苯并硫苯(DBT)。最近，DBTO已被衍生化，以研究UV-A光驱动的光脱氧在脂质、蛋白质和核酸中的作用。本研究合成了两个具有三苯基膦基团的DBTO衍生物，以促进线粒体的积累。还合成了这些衍生物的砜类似物，并将其用作荧光线粒体染料，以评估其在HeLa细胞线粒体中的定位。然后用这些衍生物通过细胞存活率测定、细胞周期时相测定和RNA-Seq分析来研究光去氧对乳腺癌细胞株MDA-MB-231的影响。DBTO衍生物被发现只有在UV-A照射后才会显着降低细胞活力，因为产生了相应的硫化物，这些硫化物被发现显著影响基因表达和细胞周期。
Photodeoxygenation of Dibenzothiophene-S-oxide (DBTO) in UV-A light produces atomic oxygen [O(3P)] and the corresponding sulfide, dibenzothiophene (DBT). Recently, DBTO has been derivatized to study the effect of UV-A light-driven photodeoxygenation in lipids, proteins, and nucleic acids. In this study, two DBTO derivatives with triphenylphosphonium groups were synthesized to promote mitochondrial accumulation. The sulfone analogs of these derivatives were also synthesized and used as fluorescent mitochondrial dyes to assess localization in mitochondria of HeLa cells. These derivatives were then used to study the effect of photodeoxygenation on MDA-MB-231 breast cancer cell line using cell viability assays, cell cycle phase determination tests, and RNA-Seq analysis. The DBTO derivatives were found to significantly decrease cell viability only after UV-A irradiation as a result of generating corresponding sulfides that were found to significantly affect gene expression and cell cycle.