Department of Chemistry, University of Malaya, 50603 Kuala Lumpur, Malaysia.
Eur J Med Chem. 2013 Sep;67:127-41. doi: 10.1016/j.ejmech.2013.06.038. Epub 2013 Jun 26.
The synthesis and characterisation of R3PAu[S2CN((i)Pr)CH2CH2OH], for R = Ph (1), Cy (2) and Et (3)4, is reported. Compounds 1-3 are cytotoxic against the doxorubicin-resistant breast cancer cell line, MCF-7R, with 1 exhibiting greater potency and cytotoxicity than either of doxorubicin and cisplatin. Based on human apoptosis PCR-array analysis, caspase activities, DNA fragmentation, cell apoptotic assays, intracellular reactive oxygen species (ROS) measurements and human topoisomerase I inhibition, induction of apoptosis by 1, and necrosis by 2 and 3, are demonstrated, by both extrinsic and intrinsic pathways. Compound 1 activates the p53 gene, 2 activates only the p73 gene, whereas 3 activates both the p53 and p73 genes. Compounds 1 and 3 activate NF-κB, and each inhibits topoisomerase I.
报告了 R3PAu[S2CN((i)Pr)CH2CH2OH]（其中 R = Ph（1）、Cy（2）和 Et（3）4）的合成和表征。化合物 1-3 对多柔比星耐药乳腺癌细胞系 MCF-7R 具有细胞毒性，化合物 1 的活性和细胞毒性均强于多柔比星和顺铂。基于人类细胞凋亡 PCR 阵列分析、半胱天冬酶活性、DNA 片段化、细胞凋亡测定、细胞内活性氧（ROS）测量和人拓扑异构酶 I 抑制，通过外在和内在途径证明了 1 通过细胞凋亡和 2 和 3 通过坏死诱导细胞凋亡。化合物 1 激活 p53 基因，2 仅激活 p73 基因，而 3 激活 p53 和 p73 基因。化合物 1 和 3 激活 NF-κB，并且每个化合物都抑制拓扑异构酶 I。
