含 2,2'-联吡啶衍生物的甲基环戊二烯基钌化合物具有很强的抗癌活性和多药耐药潜力。
Methyl-cyclopentadienyl Ruthenium Compounds with 2,2'-Bipyridine Derivatives Display Strong Anticancer Activity and Multidrug Resistance Potential.
机构信息
Centro de Química Estrutural , Faculdade de Ciências da Universidade de Lisboa , Campo Grande , 1749-016 Lisboa , Portugal.
Drug Resistance and Membrane Proteins Team , Molecular Biology and Structural Biochemistry Laboratory , UMR 5086 CNRS-UCBL1, IBCP 7 Passage du Vercors , 69 367 Lyon Cedex 07, France.
出版信息
Inorg Chem. 2018 Apr 16;57(8):4629-4639. doi: 10.1021/acs.inorgchem.8b00358. Epub 2018 Apr 3.
New ruthenium methyl-cyclopentadienyl compounds bearing bipyridine derivatives with the general formula [Ru(η-MeCp)(PPh)(4,4'-R-2,2'-bpy)] (Ru1, R = H; Ru2, R = CH; and Ru3, R = CHOH) have been synthesized and characterized by spectroscopic and analytical techniques. Ru1 crystallized in the monoclinic P2/ c, Ru2 in the triclinic P1̅, and Ru3 in the monoclinic P2/ n space group. In all molecular structures, the ruthenium center adopts a "piano stool" distribution. Density functional theory calculations were performed for all complexes, and the results support spectroscopic data. Ru1 and Ru3 were poor substrates of the main multidrug resistance human pumps, ABCB1, ABCG2, ABCC1, and ABCC2, while Ru2 displayed inhibitory properties of ABCC1 and ABCC2 pumps. Importantly, all compounds displayed a very high cytotoxic profile for ovarian cancer cells (sensitive and resistant) that was much more pronounced than that observed with cisplatin, making them very promising anticancer agents.
新型钌甲基-环戊二烯基配合物，具有一般式[Ru(η-MeCp)(PPh)(4,4'-R-2,2'-bpy)]的联吡啶衍生物（Ru1，R = H；Ru2，R = CH；和 Ru3，R = CHOH），已通过光谱和分析技术进行了合成和表征。Ru1 结晶为单斜 P2/ c，Ru2 为三斜 P1̅，Ru3 为单斜 P2/ n 空间群。在所有分子结构中，钌中心采用“钢琴凳”分布。对所有配合物都进行了密度泛函理论计算，结果支持光谱数据。Ru1 和 Ru3 是主要多药耐药性人类泵（ABCB1、ABCG2、ABCC1 和 ABCC2）的不良底物，而 Ru2 对 ABCC1 和 ABCC2 泵具有抑制作用。重要的是，所有化合物对卵巢癌细胞（敏感和耐药）均表现出非常高的细胞毒性，比顺铂观察到的毒性更为明显，这使它们成为很有前途的抗癌药物。
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