[Au(PR3)(DMT)]型四种新型磷金(I)配合物。PF6(1-4)由3-硫代氨基丁酸-丁-2-酮肟配体(TBO)和前体[Au(PR3)Cl]合成,(其中R=甲基(1),乙基(2),叔丁基(3),和苯基(4))。通过元素分析和熔点以及各种光谱技术对所得络合物进行了表征,包括FTIR和(1H,13C,和31P)NMR光谱。光谱数据证实了TBO配体与膦金(I)部分的配位。络合物1-4的溶液化学表明它们在二甲基亚砜(DMSO)和EtOH∶H2O(1∶1)的混合物中的稳定性。使用针对三种不同癌细胞系的MTT测定法相对于顺铂评估复合物的体外细胞毒性:HCT116(人结肠癌),MDA-MB-231(人类乳腺癌),和B16(鼠皮肤癌)。复合物2、3和4对所有测试的癌细胞系表现出显着的细胞毒性作用,并显示出比顺铂明显更高的活性。为了阐明磷金(I)TBO复合物的细胞毒性作用的潜在机制,采用了各种分析方法,包括线粒体膜电位,ROS生产,和基因表达分析。获得的数据表明,复合物2通过诱导氧化应激对乳腺癌细胞(MDA-MB-231)发挥有效的抗癌活性,线粒体功能障碍,和凋亡。基因表达分析表明,促凋亡基因caspase-3的活性增加,抗凋亡基因BCL-xL的活性降低,这支持了细胞凋亡发生的发现。
Four novel phosphanegold(I) complexes of the type [Au(PR3)(DMT)].PF6 (1-4) were synthesized from 3-Thiosemicarbano-butan-2-one oxime ligand (TBO) and precursors [Au(PR3)Cl], (where R = methyl (1), ethyl (2), tert-butyl (3), and phenyl (4)). The resulting complexes were characterized by elemental analyses and melting point as well as various spectroscopic techniques, including FTIR and (1H, 13C, and 31P) NMR spectroscopy. The spectroscopic data confirmed the coordination of TBO ligands to phosphanegold(I) moiety. The solution chemistry of complexes 1-4 indicated their stability in both dimethyl sulfoxide (DMSO) and a mixture of EtOH:H2O (1:1). In vitro cytotoxicity of the complexes was evaluated relative to cisplatin using an MTT assay against three different cancer cell lines: HCT116 (human colon cancer), MDA-MB-231 (human breast cancer), and B16 (murine skin cancer). Complexes 2, 3, and 4 exhibited significant cytotoxic effects against all tested cancer cell lines and showed significantly higher activity than cisplatin. To elucidate the mechanism underlying the cytotoxic effects of the phosphanegold(I) TBO complexes, various assays were employed, including mitochondrial membrane potential, ROS production, and gene expression analyses. The data obtained suggest that complex 2 exerts potent anticancer activity against breast cancer cells (MDA-MB-231) through the induction of oxidative stress, mitochondrial dysfunction, and apoptosis. Gene expression analyses showed an increase in the activity of the proapoptotic gene caspase-3 and a reduction in the activity of the antiapoptotic gene BCL-xL, which supported the findings that apoptosis had occurred.