Faculty of Chemistry, University of Wroclaw, Joliot-Curie 14, 50-383 Wroclaw, Poland.
Faculty of Chemistry, University of Wroclaw, Joliot-Curie 14, 50-383 Wroclaw, Poland.
J Inorg Biochem. 2018 Apr;181:1-10. doi: 10.1016/j.jinorgbio.2018.01.008. Epub 2018 Jan 9.
In this paper, we present a comparative study on the cytotoxic mode of action of copper(I) and copper(II) complexes with phosphine derivatives of fluoroquinolone antibiotics (ciprofloxacin HCp and norfloxacin HNr). The in vitro cytotoxic activity of four new compounds was tested against two selected cancer cell lines. All complexes exhibited much better cytotoxicity against both cell lines than unmodified fluoroquinolone antibiotics, their phosphines (PCp, PNr), chalcogenide derivatives (oxides: OPCp, OPNr; sulfides: SPCp, SPNr and selenides: SePCp, SePNr) and previously described by us complexes with phosphines derived from different fluoroquinolones: lomefloxacin (HLm) and sparfloxacin (HSf) as well as cisplatin. Apoptosis, observed at a great predominance, was induced by all studied complexes. Importantly, it was concluded that coordination compounds with Cu(I) ion ([Cu-PNr] and [Cu-PCp]) were much more active than those with Cu(II) ion ([OPNr-Cu], [OPCp-Cu]), even though the highest efficacy to produce reactive oxygen species, participating in overall cytotoxicity, was proved for copper(II) complexes among all studied compounds. Herein, we discuss not only results obtained for copper(I)/(II) complexes with phosphines derived from HNr and HCp but we also compare them to previously described data for complexes with HLm and HSf derivatives. This is the first insight into a structure-activity relationship of copper complexes with phosphine derivatives of fluoroquinolone antibiotics.
在本文中，我们对铜（I）和铜（II）配合物与氟喹诺酮类抗生素（环丙沙星 HCP 和诺氟沙星 HNR）的膦衍生物的细胞毒性作用模式进行了比较研究。四种新化合物的体外细胞毒性活性针对两种选定的癌细胞系进行了测试。所有配合物对两种细胞系的细胞毒性均明显优于未修饰的氟喹诺酮类抗生素、其膦（PCp、PNr）、硫属元素衍生物（氧化物：OPCp、OPNr；硫化物：SPCp、SPNr 和硒化物：SePCp、SePNr）以及我们之前描述的由不同氟喹诺酮类抗生素衍生的膦配合物：洛美沙星（HLm）和司帕沙星（HSf）以及顺铂。观察到的凋亡在很大程度上是由所有研究的配合物诱导的。重要的是，得出结论，与 Cu(II)离子（[OPNr-Cu]、[OPCp-Cu]）配位的配合物比与 Cu(I)离子（[Cu-PNr]和[Cu-PCp]）配位的配合物活性更高，尽管所有研究化合物中铜（II）配合物被证明具有产生参与总体细胞毒性的活性氧物种的最高功效。在这里，我们不仅讨论了源自 HNr 和 HCp 的膦衍生物的铜（I）/（II）配合物的结果，还将它们与先前描述的 HLm 和 HSf 衍生物配合物的数据进行了比较。这是首次深入研究铜配合物与氟喹诺酮类抗生素的膦衍生物的结构-活性关系。
