Anti‐proliferative potential of copper(I) acylthiourea complexes with triphenylphosphine against breast cancer cells
Anti‐proliferative potential of copper(I) acylthiourea complexes with triphenylphosphine against breast cancer cells
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铜（I）酰基硫脲与三苯基膦配合物对乳腺癌细胞的抗增殖潜力
DOI：
10.1002/aoc.7087
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发表时间：
2023
影响因子：
3.9
通讯作者：
R. Karvembu
中科院分区：
文献类型：
--
作者：
D. P. Dorairaj;J. Haribabu;D. Mahendiran;R. Malekshah;S. C. Hsu;R. Karvembu
合成了5个新的酰基硫脲铜配合物（C1-C5），通式为[Cu（L-R）Cl（PPh 3）2] [L =单齿酰基硫脲配体，R = C6 H5（L1），C6 H4 CH 3（o）（L2），C6 H4 OCH 2CH 3（p）（L3），C10 H7（L4）或C6 H4 Cl（p）（L5）].所有的配合物进行了表征分析和光谱工具。配合物（C1-C5）表现出扭曲的四面体几何形状，如从单晶X射线衍射研究推断的。复合物进行相互作用的生物分子（小牛胸腺[CT] DNA/牛血清白蛋白[BSA]）;轴承萘基取代基（C4）表现出最高的结合效率。此外，专门针对乳腺癌细胞系，即MCF 7、T47 D和MDA MB 231研究了复合物的抗癌活性。ComplexC 4对三种癌细胞株均具有较强的细胞毒活性，IC_（50）分别为0.75、0.75和0.68 μM。方便地，复合物显示出对正常MCF 10a人乳腺细胞的四倍小的毒性。采用吖啶橙子/溴化乙锭（AO/EB）和Hoechst 33258染色法检测复合物C4诱导细胞凋亡的能力。此外，还发现complex C4通过活性氧介导的线粒体信号通路诱导细胞凋亡。共聚焦荧光显微镜观察发现，complex C4主要定位于线粒体，Western blot分析证实complex C4可诱导MDA MB 231细胞凋亡。
We report the synthesis of five new Cu(I) acylthiourea complexes (C1–C5) bearing the general formula [Cu(L‐R)Cl (PPh3)2] [L = monodentate acylthiourea ligand, R = C6H5(L1), C6H4CH3(o) (L2), C6H4OCH2CH3(p) (L3), C10H7(L4) or C6H4Cl(p) (L5)]. All the complexes were characterized by analytical and spectroscopic tools. The complexes (C1–C5) exhibited a distorted tetrahedral geometry as inferred from the single crystal X‐ray diffraction study. The complexes were subjected to interact with the biomolecules (calf thymus [CT] DNA/bovine serum albumin [BSA]); the one bearing naphthyl substituent (C4) exhibited the highest binding efficacy. Further, anticancer activity of the complexes was studied exclusively against breast cancer cell lines, namely, MCF7, T47D, and MDA MB 231. ComplexC4was found to be highly cytotoxic on the three cancer cell lines with the IC50values of 0.75, 0.75, and 0.68 μM, respectively. Conveniently, the complexes displayed fourfold less toxicity against the normal MCF10a human breast cells. The ability of complexC4to induce apoptosis was analyzed by acridine orange/ethidium bromide (AO/EB) and Hoechst 33258 staining assays. Furthermore, it was found that complexC4induced apoptosis via reactive oxygen species (ROS)‐mediated mitochondrial signaling pathway. Confocal fluorescence images of the cells subjected to lyso and mitotracker staining assays revealed that complexC4was primarily localized on the mitochondria, and finally, Western blot analysis also confirmed the apoptosis induced by complexC4in the MDA MB 231 cancer cells.