Centre for Advanced Materials & Industrial Chemistry (CAMIC), School of Science, RMIT University, GPO BOX 2476, Melbourne, 3001, Australia.
Applied Biology Division, CSIR-Indian Institute of Chemical Technology, Hyderabad, India.
Chemistry. 2019 Nov 7;25(62):14089-14100. doi: 10.1002/chem.201903388. Epub 2019 Sep 30.
Four cycloaurated phosphine sulfide complexes, [Au{κ -2-C H P(S)Ph } ][AuX ] [X=Cl (2), Br (3), I (4)] and [Au{κ -2-C H P(S)Ph } ]PF (5), have been prepared and thoroughly characterized. The compounds were found to be stable under physiological-like conditions and showed excellent cytotoxicity against a broad range of cancer cell lines and remarkable cytotoxicity in 3D tumor spheroids. Mechanistic studies with cervical cancer (HeLa) cells indicated that the cytotoxic effects of the compounds involve the inhibition of thioredoxin reductase and induction of apoptosis through mitochondrial disruption. In vivo experiments in nude mice bearing HeLa xenografts showed that treatment with compounds 4 and 5 resulted in significant inhibition of tumor growth (35.8 and 46.9 %, respectively), better than that of cisplatin (29 %). The newly synthesized gold complexes were also evaluated for their in vitro and in vivo anti-inflammatory activity through the study of lipopolysaccharide (LPS)-activated macrophages and carrageenan-induced hind paw edema in rats, respectively.
已制备并充分表征了四个环金膦硫配合物[Au{κ -2-C H P(S)Ph } ][AuX ]（X=Cl（2），Br（3），I（4））和[Au{κ -2-C H P(S)Ph } ]PF （5）。这些化合物在生理条件下稳定，并对广泛的癌细胞系表现出优异的细胞毒性，对 3D 肿瘤球体的细胞毒性也非常显著。用宫颈癌（HeLa）细胞进行的机制研究表明，这些化合物的细胞毒性作用涉及到硫氧还蛋白还原酶的抑制和通过线粒体破坏诱导细胞凋亡。在荷 HeLa 异种移植瘤的裸鼠体内实验中，化合物 4 和 5 的治疗导致肿瘤生长显著抑制（分别为 35.8%和 46.9%），优于顺铂（29%）。通过研究脂多糖（LPS）激活的巨噬细胞和角叉菜胶诱导的大鼠后爪水肿，还分别评估了新合成的金配合物的体外和体内抗炎活性。
