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含二苯基膦甲烷和喹啉羧酸盐的阳离子钌(II)配合物的合成、表征、细胞毒性活性及其与CT-DNA和BSA的相互作用

Synthesis, Characterization, Cytotoxic Activity, and Interactions with CT-DNA and BSA of Cationic Ruthenium(II) Complexes Containing Dppm and Quinoline Carboxylates.

作者信息

da Silva Edinaldo N, da Silva Paulo A B, Graminha Angélica E, de Oliveira Pollyanna F, Damasceno Jaqueline L, Tavares Denise C, Batista Alzir A, Von Poelhsitz Gustavo

机构信息

Instituto de Química, Universidade Federal de Uberlândia, 38400-902 Uberlândia, MG, Brazil.

Departamento de Química, Universidade Federal de São Carlos, 13565-905 São Carlos, SP, Brazil.

出版信息

Bioinorg Chem Appl. 2017;2017:2562780. doi: 10.1155/2017/2562780. Epub 2017 Jul 26.

Abstract

The complexes -[Ru(quin)(dppm)]PF and -[Ru(kynu)(dppm)]PF (quin = quinaldate; kynu = kynurenate; dppm = (diphenylphosphino)methane) were prepared and characterized by elemental analysis, electronic, FTIR, H, and P{H} NMR spectroscopies. Characterization data were consistent with a arrangement for the dppm ligands and a bidentate coordination through carboxylate oxygens of the quin and kynu anions. These complexes were not able to intercalate CT-DNA as shown by circular dichroism spectroscopy. On the other hand, bovine serum albumin (BSA) binding constants and thermodynamic parameters suggest spontaneous interactions with this protein by hydrogen bonds and van der Waals forces. Cytotoxicity assays were carried out on a panel of human cancer cell lines including HepG2, MCF-7, and MO59J and one normal cell line GM07492A. In general, the new ruthenium(II) complexes displayed a moderate to high cytotoxicity in all the assayed cell lines with IC ranging from 10.1 to 36 M and were more cytotoxic than the precursor -[RuCl(dppm)]. The -[Ru(quin)(dppm)]PF were two to three times more active than the reference metallodrug cisplatin in the MCF-7 and MO59J cell lines.

摘要

制备了配合物-[Ru(喹啉)(二苯基膦甲烷)]PF和-[Ru(犬尿喹啉酸)(二苯基膦甲烷)]PF(喹啉=喹哪啶;犬尿喹啉酸=犬尿喹啉酸;二苯基膦甲烷=dppm),并通过元素分析、电子光谱、傅里叶变换红外光谱、氢谱和磷{氢}核磁共振光谱对其进行了表征。表征数据与二苯基膦甲烷配体的排列以及通过喹啉和犬尿喹啉酸阴离子的羧酸根氧进行的双齿配位一致。圆二色光谱表明,这些配合物无法嵌入CT-DNA。另一方面,牛血清白蛋白(BSA)结合常数和热力学参数表明,它们通过氢键和范德华力与该蛋白质发生自发相互作用。对包括HepG2、MCF-7和MO59J在内的一组人类癌细胞系和一个正常细胞系GM07492A进行了细胞毒性试验。总体而言,新的钌(II)配合物在所有检测的细胞系中均表现出中度至高细胞毒性,IC范围为10.1至36μM,并且比前体-[RuCl(dppm)]更具细胞毒性。-[Ru(喹啉)(dppm)]PF在MCF-7和MO59J细胞系中的活性比参考金属药物顺铂高两到三倍。

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