Organic Chemistry Laboratory, University of Bayreuth, Universitaetsstrasse 30, D-95440 Bayreuth, Germany.
Steroids. 2011 Mar;76(4):393-9. doi: 10.1016/j.steroids.2010.12.009. Epub 2010 Dec 22.
(Arene)dichloridoruthenium(II) complexes with N-coordinated isonicotinates of androgens (6) and estrogens (9) were prepared and tested for affinity to the estrogen receptor (ERα) and sex hormone binding globulin (SHBG), as well as for cytotoxicity in cancer cells. None of the new complexes bound noticeably to the ER and most of them also bound less strongly to SHBG than the corresponding unmetallated steroids 7. In MTT assays the Ru(p-cymene) complexes 9 of 2-substituted estrones were equally or even more cytotoxic than the metal-free steroids against hormone-dependent (MCF-7 breast and KB-V1 cervix carcinomas) and hormone-independent (518A2 melanoma) cells. The addition of external SHBG to MTT assays lowered the cytotoxicities of the complexes 9 and distinctly more so those of some steroids 7, probably by the way of sequestration and reduction of the cellular uptake. In the absence of SHBG the estrogen complexes 9 were internalized by 518A2 melanoma cells and ruthenated their DNA as quantified by ICP-OES. They also ruthenated salmon sperm DNA but did not change the topology of plasmid DNA in EMSA experiments. In addition, the Ru(p-cymene) complex of 2-ethoxyestrone (9c) was shown to reduce the motility of 518A2 melanoma cells in a wound-healing assay.
（芳基）二氯合钌（II）配合物与雄激素（6）和雌激素（9）的 N 配位异烟酸酯被制备并测试其对雌激素受体（ERα）和性激素结合球蛋白（SHBG）的亲和力，以及对癌细胞的细胞毒性。新的配合物中没有一种明显与 ER 结合，而且大多数与 SHBG 的结合强度也低于相应的未配位类固醇 7。在 MTT 测定中，2-取代雌酮的 Ru(p-cymene)配合物 9 对依赖激素的（MCF-7 乳腺癌和 KB-V1 宫颈癌）和非依赖激素的（518A2 黑素瘤）细胞的细胞毒性与无金属的类固醇相等或甚至更强。在 MTT 测定中添加外部 SHBG 会降低配合物 9 的细胞毒性，而对某些类固醇 7 的降低作用更为明显，这可能是通过隔离和减少细胞摄取来实现的。在没有 SHBG 的情况下，雌激素配合物 9 被 518A2 黑素瘤细胞内化，并通过 ICP-OES 定量检测到其 DNA 被钌化。它们还钌化鲑鱼精子 DNA，但在 EMSA 实验中不会改变质粒 DNA 的拓扑结构。此外，2-乙氧基雌酮（9c）的 Ru(p-cymene)配合物被证明可以减少 518A2 黑素瘤细胞在划痕愈合测定中的迁移能力。
