Ru(II)-Based Acetylacetonate Complexes Induce Apoptosis Selectively in Cancer Cells
Ru(II)-Based Acetylacetonate Complexes Induce Apoptosis Selectively in Cancer Cells
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DOI：
10.1021/acs.inorgchem.1c02796
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发表时间：
2021-12-20
影响因子：
4.6
通讯作者：
Kodanko, Jeremy J.
中科院分区：
文献类型：
--
作者：
Gupta, Sayak;Vandevord, Jessica M.;Kodanko, Jeremy J.
报道了7个含乙酰丙酮(Acac)配体的Ru(II)多吡啶配合物的合成、化学和生物表征。测量了电子吸收光谱和Ru(III/II)对在+0.60~+0.73V对Ag/AgCl的电化学势。筛选了一系列化合物对MDA-MB-231、DU-145和MCF-10A细胞株的抑制作用，以评价其对肿瘤细胞和正常细胞的细胞毒作用。虽然大多数配合物对癌细胞和正常细胞系都是无毒或等价的，但化合物1[Ru(Dpqy)(Acac)(Py)](Pf6)，其中dqpy是2，6-二(喹啉-2-基)吡啶，与正常细胞相比，对癌症的选择性高达2.5：1.0，在MDA-MB-231细胞中显示出纳米分子的EC50值。亲脂性测定为辛醇/水分配系数logP-o/w，范围为-0.33(0.06)至1.15(0.10)。尽管细胞毒性与电化学势无关，但亲脂性与毒性之间存在适度的线性相关。细胞死亡机制研究表明，包括1在内的几个Ru-acac化合物可诱导MDA-MB-231细胞凋亡。
The synthesis, chemical and biological characterization of seven Ru(II) polypyridyl complexes containing acetylacetonate (acac) ligands are reported. Electronic absorption spectra were determined and electrochemical potentials consistent with Ru(III/II) couples ranging from +0.60 to +0.73 V vs Ag/AgCl were measured. A series of complexes were screened against MDA-MB-231, DU-145, and MCF-10A cell lines to evaluate their cytotoxicities in cancer and normal cell lines. Although most complexes were either nontoxic or equipotent in cancer cells and normal cell lines, compound 1, [Ru(dpqy)(acac)(py)](PF6), where dqpy is 2,6-di(quinolin-2-yl)pyridine, showed up to 2.5:1.0 selectivity for cancer as compared to normal cells, along with nanomolar EC50 values in MDA-MB-231 cells. Lipophilicity, determined as the octanol/water partition coefficient, log P-o/w, ranged from -0.33 (0.06) to 1.15 (0.10) for the complexes. Although cytotoxicity was not correlated with electrochemical potentials, a moderate linear correlation between lipophilicity and toxicities was observed. Cell death mechanism studies indicated that several of the Ru-acac compounds, including 1, induce apoptosis in MDA-MB-231 cells.