a Department of Organic Chemistry, School of Pharmacy with the Division of Laboratory Medicine , The Medical University of Silesia , Sosnowiec , Poland.
b Department of Cell Biology, School of Pharmacy with the Division of Laboratory Medicine , The Medical University of Silesia , Sosnowiec , Poland.
J Enzyme Inhib Med Chem. 2019 Dec;34(1):1298-1306. doi: 10.1080/14756366.2019.1639695.
10-1,9-diazaphenothiazine was obtained in the sulphurisation reaction of diphenylamine with elemental sulphur and transformed into new 10-substituted derivatives, containing alkyl and dialkylaminoalkyl groups at the thiazine nitrogen atom. The 1,9-diazaphenothiazine ring system was identified with advanced H and C NMR techniques (COSY, NOESY, HSQC and HMBC) and confirmed by X-ray diffraction analysis of the methyl derivative. The compounds exhibited significant anticancer activities against the human glioblastoma SNB-19, melanoma C-32 and breast cancer MDA-MB-231 cell lines. The most active 1,9-diazaphenothiazines were the derivatives with the propynyl and , -diethylaminoethyl groups being more potent than cisplatin. For those two compounds, the expression of , , , and genes was detected by the RT-QPCR method. The proteome profiling study showed the most probable compound action on SNB-19 cells through the intrinsic mitochondrial pathway of apoptosis. The 1,9-diazaphenotiazine system seems to be more potent than known isomeric ones (1,6-diaza-, 1,8-diaza-, 2,7-diaza- and 3,6-diazaphenothiazine).
10-1,9-二氮杂菲并噻嗪是由二苯胺与元素硫的硫化反应得到的,并转化为新的 10 位取代衍生物,噻嗪氮原子上含有烷基和二烷基氨基烷基。通过先进的 H 和 C NMR 技术(COSY、NOESY、HSQC 和 HMBC)鉴定了 1,9-二氮杂菲并噻嗪环系统,并通过对甲基衍生物的 X 射线衍射分析得到了证实。这些化合物对人类神经胶质瘤 SNB-19、黑色素瘤 C-32 和乳腺癌 MDA-MB-231 细胞系表现出显著的抗癌活性。最具活性的 1,9-二氮杂菲并噻嗪衍生物是具有炔丙基和, -二乙氨基乙基的衍生物,其活性强于顺铂。对于这两种化合物,通过 RT-QPCR 方法检测了,,, 和 基因的表达。蛋白质组谱研究表明,该化合物最有可能通过内在的线粒体凋亡途径作用于 SNB-19 细胞。1,9-二氮杂菲并噻嗪系统似乎比已知的异构体(1,6-二氮杂、1,8-二氮杂、2,7-二氮杂和 3,6-二氮杂菲并噻嗪)更有效。