Stephens Liam J, Levina Aviva, Trinh Iman, Blair Victoria L, Werrett Melissa V, Lay Peter A, Andrews Philip C
School of Chemistry, Monash University, 14 Rainforest Walk, Clayton, VIC, 3800, Australia.
School of Chemistry, University of Sydney, Eastern Avenue, Sydney, NSW, 2006, Australia.
Chembiochem. 2020 Apr 17;21(8):1188-1200. doi: 10.1002/cbic.201900676. Epub 2019 Dec 12.
Ru -arene complexes provide a versatile scaffold for novel anticancer drugs. Seven new Ru -arene-thiocarboxylato dimers were synthesized and characterized. Three of the complexes (2 a, b and 5) showed promising antiproliferative activities in MDA-MB-231 (human invasive breast cancer) cells, and were further tested in a panel of fifteen cancerous and noncancerous cell lines. Complex 5 showed moderate but remarkably selective activity in MDA-MB-231 cells (IC =39±4 μm Ru). Real-time proliferation studies showed that 5 induced apoptosis in MDA-MB-231 cells but had no effect in A549 (human lung cancer, epithelial) cells. By contrast, 2 a and b showed moderate antiproliferative activity, but no apoptosis, in either cell line. Selective cytotoxicity of 5 in aggressive, mesenchymal-like MDA-MB-231 cells over many common epithelial cancer cell lines (including noninvasive breast cancer MCF-7) makes it an attractive lead compound for the development of specifically antimetastatic Ru complexes with low systemic toxicity.
钌芳烃配合物为新型抗癌药物提供了一种多功能支架。合成并表征了七种新型钌芳烃 - 硫代羧酸盐二聚体。其中三种配合物（2a、b和5）在MDA - MB - 231（人侵袭性乳腺癌）细胞中显示出有前景的抗增殖活性，并在一组十五种癌细胞和非癌细胞系中进一步测试。配合物5在MDA - MB - 231细胞中显示出中等但显著的选择性活性（IC = 39±4 μM Ru）。实时增殖研究表明，5诱导MDA - MB - 231细胞凋亡，但对A549（人肺癌，上皮细胞）细胞无影响。相比之下，2a和b在两种细胞系中均显示出中等抗增殖活性，但无凋亡现象。5在侵袭性、间充质样MDA - MB - 231细胞中对许多常见上皮癌细胞系（包括非侵袭性乳腺癌MCF - 7）具有选择性细胞毒性，这使其成为开发具有低全身毒性的特异性抗转移钌配合物的有吸引力的先导化合物。
