Department of Chemistry, University of Warwick, Gibbet Hill Road, Coventry CV4 7AL, UK.
J Med Chem. 2010 Jan 28;53(2):840-9. doi: 10.1021/jm901556u.
The cytotoxicity, hydrophobicity (log P), cellular uptake, aqueous reactivity, and extent of DNA adduct formation in the A2780 ovarian carcinoma cells for four osmium(II) arene complexes [(eta(6)-arene)Os(4-methyl-picolinate)Cl] that differ only in their arene ligands as benzene (1), p-cymene (2), biphenyl (3), or tetrahydroanthracene (4) are reported. There is a correlation between hydrophobicity (log P), cellular uptake, nucleus uptake, and cytotoxicity of the complexes, following the order 3 approximately 4 > 2 > 1, suggesting that the arene plays an important role in the biological activity of these types of compounds. Cell distribution studies using fractionation showed that all four compounds distribute similarly within cells. DNA binding of osmium did not correlate with cytotoxicity, indicating that the nature of the DNA lesion may also be crucial to activity. TEM images of ovarian cells treated with 3 revealed morphological changes associated with apoptosis with possible involvement of mitochondria.
报道了四种顺式-[（η6-芳烃）Os（4-甲基吡啶甲酸盐）Cl]钌（II）芳环配合物在 A2780 卵巢癌细胞中的细胞毒性、疏水性（log P）、细胞摄取、水反应性、DNA 加合物形成程度，它们仅在芳环配体上有所不同，分别为苯（1）、对伞花烃（2）、联苯（3）或四氢蒽（4）。疏水性（log P）、细胞摄取、核摄取和复合物的细胞毒性之间存在相关性，其顺序为 3 约 4 > 2 > 1，表明芳环在这类化合物的生物活性中起着重要作用。使用分级分离的细胞分布研究表明，所有四种化合物在细胞内的分布相似。奥斯姆与 DNA 的结合与细胞毒性无关，表明 DNA 损伤的性质对活性也可能至关重要。用 3 处理卵巢细胞的 TEM 图像显示与细胞凋亡相关的形态变化，可能涉及线粒体。
