Ruthenium-Arene Complexes of Curcumin: X-Ray and Density Functional Theory Structure, Synthesis, and Spectroscopic Characterization, in Vitro Antitumor Activity, and DNA Docking Studies of (p-Cymene)Ru(curcuminato)chloro
Ruthenium-Arene Complexes of Curcumin: X-Ray and Density Functional Theory Structure, Synthesis, and Spectroscopic Characterization, in Vitro Antitumor Activity, and DNA Docking Studies of (p-Cymene)Ru(curcuminato)chloro
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DOI：
10.1021/jm200912j
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发表时间：
2012-02-09
影响因子：
7.3
通讯作者：
Pettinari, Claudio
中科院分区：
文献类型：
--
作者：
Caruso, Francesco;Rossi, Miriam;Pettinari, Claudio
标题化合物对五种肿瘤细胞系的体外抗增殖活性显示出对结肠直肠肿瘤HCT 116的优先性，IC 50 = 13.98 μ M，其次是乳腺MCF 7（19.58 μ M）和卵巢A2780（23.38 μ M）细胞系;人胶质母细胞瘤U-87和肺癌A549的敏感性较低。用一种含有去甲氧基和双去甲氧基姜黄素的姜黄素试剂合成了标题化合物，并分离得到了氯代（对伞花烃）钌（去甲氧基姜黄素）。标题化合物的晶体结构表明：（1）氯原子通过氢键与两个O-（羟基）连接，形成无限的两步网络;（2）姜黄素基有明显的扭曲，两个苯环平面之间有20度的扭曲。这也见于Ru-复合物与富含鸟嘌呤B-DNA十聚体的对接，其中检测到Ru-N7（鸟嘌呤）相互作用。这种Ru-N7（鸟嘌呤）相互作用也可以在Ru-络合物-鸟苷衍生物上用ESI-MS观察到。
The in vitro antiproliferative activity of the title compound on five tumor cell lines shows preference for the colon-rectal tumor HCT116, IC50 = 13.98 mu M, followed by breast MCF7 (19.58 mu M) and ovarian A2780 (23.38 mu M) cell lines; human glioblastoma U-87 and lung carcinoma A549 are less sensitive. A commercial curcumin reagent, also containing demethoxy and bis-demethoxy curcumin, was used to synthesize the title compound, and so (p-cymene)Ru(demethoxycurcuminato)chloro was also isolated and chemically characterized. The crystal structure of the title compound shows (1) the chlorine atom linking two neighboring complexes through H-bonds with two O-(hydroxyl), forming an infinite two-step network; (2) significant twist in the curcuminato, 20 degrees between the planes of the two phenyl rings. This was also seen in the docking of the Ru-complex onto a rich guanine B-DNA decamer, where a Ru-N7(guanine) interaction is detected. This Ru-N7(guanine) interaction is also seen with ESI-MS on a Ru-complex-guanosine derivative.