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新型钌(II)芳烃配合物与色酮衍生物的合成、亲脂性及细胞毒性作用

The synthesis, lipophilicity and cytotoxic effects of new ruthenium(II) arene complexes with chromone derivatives.

作者信息

Pastuszko Adam, Majchrzak Kinga, Czyz Malgorzata, Kupcewicz Bogumiła, Budzisz Elzbieta

机构信息

Department of Cosmetic Raw Materials Chemistry, Faculty of Pharmacy, Medical University of Lodz, Muszynskiego 1, 90-151 Lodz, Poland.

Department of Molecular Biology of Cancer, Medical University of Lodz, Mazowiecka 6/8, 92-215 Lodz, Poland.

出版信息

J Inorg Biochem. 2016 Jun;159:133-41. doi: 10.1016/j.jinorgbio.2016.02.020. Epub 2016 Feb 26.

Abstract

A series of arene ruthenium(II) complexes with the general formula [(η(6)-arene)Ru(L)X2] (where arene=p-cymene, benzene, hexamethylbenzene or mesitylene, L=aminoflavone or aminochromone derivatives and X=Cl, I) were synthesized and characterized by elemental analysis, MS, IR and (1)H NMR spectroscopy. The stability of the selected complexes was assessed by UV-Vis spectroscopy in 24-hour period. The lipophilicity of the synthesized complexes was determined by the shake-flask method, and their cytotoxicity evaluated in vitro on patient-derived melanoma populations. The most active complexes against melanoma cells contain 7-aminoflavone and 6-aminoflavone as a ligand. The relationship between the cytotoxicity of all the obtained compounds and their logP values was determined and briefly analyzed with two different patterns observed.

摘要

合成了一系列通式为[(η(6)-芳烃)Ru(L)X2]的芳烃钌(II)配合物(其中芳烃 = 对异丙基苯、苯、六甲基苯或均三甲苯,L = 氨基黄酮或氨基色酮衍生物,X = Cl、I),并通过元素分析、质谱、红外光谱和(1)H核磁共振光谱对其进行了表征。通过紫外可见光谱在24小时内评估所选配合物的稳定性。采用摇瓶法测定合成配合物的亲脂性,并在体外对患者来源的黑色素瘤群体评估其细胞毒性。对黑色素瘤细胞活性最高的配合物含有7-氨基黄酮和6-氨基黄酮作为配体。确定了所有所得化合物的细胞毒性与其logP值之间的关系,并以观察到的两种不同模式进行了简要分析。

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