Water-Soluble Ruthenium(II) Complexes with Chiral 442,3-Dihydroxypropyl)-formamide Oxoaporphine (FOA): In Vitro and in Vivo Anticancer Activity by Stabilization of G-Quadruplex DNA, Inhibition of Telomerase Activity, and Induction of Tumor Cell Apoptosis
Water-Soluble Ruthenium(II) Complexes with Chiral 442,3-Dihydroxypropyl)-formamide Oxoaporphine (FOA): In Vitro and in Vivo Anticancer Activity by Stabilization of G-Quadruplex DNA, Inhibition of Telomerase Activity, and Induction of Tumor Cell Apoptosis
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水溶性钌 (II) 与手性 4-(2,3-二羟丙基)-甲酰胺氧代阿泊啡 (FOA) 的复合物：通过稳定 G-四链体 DNA、抑制端粒酶活性和诱导肿瘤来实现体外和体内抗癌活性
DOI：
10.1021/acs.jmedchem.5b00444
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发表时间：
2015-06-11
影响因子：
7.3
通讯作者：
Liang, Hong
中科院分区：
文献类型：
--
作者：
Chen, Zhen-Feng;Qin, Qi-Pin;Liang, Hong
Three water-soluble ruthenium(II) complexes with chiral 4-(2,3-dihydroxypropyl)-formamide oxoaporphine (FOA) were synthesized and characterized. It was found that these ruthenium(II) complexes exhibited considerable in vitro anticancer activities and that they were the effective stabilizers of telomeric and G-quadruplex-DNA (G4-DNA) in promoter of c-myc, which acted as a telomerase inhibitor targeting G4-DNA and induced cell senescence and apoptosis. Interestingly, the in vitro anticancer activity of 6 (LC-003) was higher than those of 4 (LC-001) and 5 (LC-002), more selective for BEL-7404 cells than for normal HL-7702 cells, and preferred to activate caspases-3/9. The different biological behaviors of the ruthenium complexes could be correlated with the chiral nature of 4-(2,3-dihydroxypropyl)-formamide oxoaporphine. More significantly, 6 exhibited effective inhibitory on tumor growth in BEL-7402 xenograft mouse model and higher in vivo safety than cisplatin. These mechanistic insights indicate that 6 displays low toxicity and can be a novel anticancer drug candidate.
