Synthesis, Characterization, and Antitumor Activity of Water-Soluble (Arene)ruthenium(II) Derivatives of 1,3-Dimethyl-4-acylpyrazolon-5-ato Ligands. First Example of Ru(arene)(ligand) Antitumor Species Involving Simultaneous Ru-N7(guanine) Bonding and Ligand Intercalation to DNA
Synthesis, Characterization, and Antitumor Activity of Water-Soluble (Arene)ruthenium(II) Derivatives of 1,3-Dimethyl-4-acylpyrazolon-5-ato Ligands. First Example of Ru(arene)(ligand) Antitumor Species Involving Simultaneous Ru-N7(guanine) Bonding and Ligand Intercalation to DNA
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DOI：
10.1021/ic403170y
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发表时间：
2014-04-07
影响因子：
4.6
通讯作者：
Marchetti, Fabio
中科院分区：
文献类型：
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作者：
Caruso, Francesco;Monti, Elena;Marchetti, Fabio
本文报道了新型水溶性[（芳烃）Ru-II（Q）Cl]和[（芳烃）Ru-II（Q）（X）] BF_4化合物的合成（芳烃=对伞花烃、苯、六甲基; HQ = 1，3-二甲基-4-R-（C=O）-5-吡唑啉酮，HQ（Me），R =甲基，HQ（Ph），R =苯基，HQ（Naph），R =萘基; X = H2O，9-乙基鸟嘌呤），以及它们对细胞系MCF 7的体外抗肿瘤活性（HTB-22，人乳腺癌），HCT 116（CCL-247，人结肠直肠癌）、A2780（人卵巢癌）、A549（CCL-185，人肺癌）和U87 MG（HTB-1，人胶质母细胞瘤）。测定了两种配合物的X-射线晶体结构。其中之一，{氯-（p-cymene）-[（1，3-二甲基-4-（1-萘甲酰基）-吡唑啉酮-5-ato]钌（II）}，也研究了密度泛函理论方法，并选择为对接的DNA八聚体之间的DNA碱基插入的萘基部分和Ru-N7（鸟嘌呤）键。
We report on the synthesis of novel water-soluble [(arene)Ru-II(Q)Cl] and [(arene)Ru-II(Q)(X)]BF4 compounds (arene = p-cymene, benzene, hexamethylbenzene; HQ = 1,3-dimethyl-4-R-(C=O)-5-pyrazolone, HQ(Me), R = methyl, HQ(Ph), R = phenyl, HQ(Naph), R = naphthyl; X = H2O, 9-ethylguanine), and their in vitro antitumor activity toward the cell lines MCF7 (HTB-22, human breast adenocarcinoma), HCT116 (CCL-247, human colorectal carcinoma), A2780 (human ovarian carcinoma), A549 (CCL-185, human lung carcinoma), and U87 MG (HTB-1, human glioblastoma). The X-ray crystal structures of two complexes were determined. One of them, {chlorido-(p-cymene)-[(1,3-dimethyl-4-(1-naphthoyl)-pyrazolon-5-ato]ruthenium(II)}, was also studied with density functional theory methods and was selected for docking on a DNA octamer showing intercalation between DNA bases by the naphthyl moiety and for Ru-N7(guanine) bonding.