Zieba Andrzej, Kozik Violetta, Suwinska Kinga, Kawulok Agata, Pluta Tadeusz, Jampilek Josef, Bak Andrzej
Department of Organic Chemistry, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, Jagiellonska 4, 41-200 Sosnowiec, Poland.
Institute of Chemistry, University of Silesia, Szkolna 9, 40-007 Katowice, Poland.
Molecules. 2024 Sep 12;29(18):4337. doi: 10.3390/molecules29184337.
In this work, the synthesis, structural analysis and anticancer properties of 5-methyl-9-trifluoromethyl-12-quino[3,4-][1,4]benzothiazinium chloride () are described. Compound was synthesized by reacting 1-methyl-4-butylthio-3-(benzoylthio)quinolinium chloride with 4-(trifluoromethyl)aniline, respectively. The structure of the resulting product was determined using H-NMR and C-NMR spectroscopy as well as HR-MS spectrometry. The spatial geometry of agent and the arrangement of molecules in the crystal (unit cell) were also confirmed using X-ray diffraction. The tetracyclic quinobenzothiazinium system is fairly planar because the dihedral angle between the planes formed by the benzene ring and the quinoline system is 173.47°. In order to obtain insight into the electronic charge distribution of the investigated molecule, electronic structure calculations employing the Density Functional Theory (DFT) were performed. Moreover, antiproliferative activity against a set of pancreatic cancer cell lines was tested, with compound showing IC values against human primary pancreatic adenocarcinoma BxPC-3 and human epithelioid pancreatic carcinoma Panc-1 of 0.051 µM and 0.066 µM, respectively. The IC value of cytotoxicity/cell viability of the investigated compound assessed on normal human lung fibroblasts WI38 was 0.36 µM.
在本研究中，描述了5-甲基-9-三氟甲基-12-喹啉并[3,4-][1,4]苯并噻嗪鎓氯化物（）的合成、结构分析及抗癌特性。化合物是通过使1-甲基-4-丁硫基-3-（苯甲硫基）喹啉鎓氯化物分别与4-（三氟甲基）苯胺反应合成的。使用¹H-NMR和¹³C-NMR光谱以及高分辨质谱法确定了所得产物的结构。还使用X射线衍射确认了试剂的空间几何形状以及晶体（晶胞）中分子的排列。四环喹啉并苯并噻嗪鎓体系相当平面，因为苯环和喹啉体系形成的平面之间的二面角为173.47°。为了深入了解所研究分子的电子电荷分布，采用密度泛函理论（DFT）进行了电子结构计算。此外，测试了对一组胰腺癌细胞系的抗增殖活性，化合物对人原发性胰腺腺癌BxPC-3和人上皮样胰腺癌Panc-1的IC值分别为0.051μM和0.066μM。在所研究化合物对正常人肺成纤维细胞WI38的细胞毒性/细胞活力的IC值为0.36μM。
