Katsarou Maria E, Efthimiadou Eleni K, Psomas George, Karaliota Alexandra, Vourloumis Dionisios
Laboratory for Chemical Biology, Institute of Physical Chemistry, NCSR Demokritos, Paraskevi Attikis, Greece.
J Med Chem. 2008 Feb 14;51(3):470-8. doi: 10.1021/jm7013259. Epub 2008 Jan 19.
We have synthesized and characterized a novel copper(II) complex of the fluoroquinolone antibacterial drug N-propyl-norfloxacin (Hpr-norf) in the presence of 1,10-phenanthroline (Phen) and studied its biological properties as antitumor antibiotic and antimicrobial agent. Human acute myeloid leukemia cell line HL-60, MTT assay, and Trypan blue assay were used to test the antileukemic, the cell viability, and the structural integrity of the cell membrane and cell proliferation properties of (chloro)(Phen)( N-propyl-norfloxacinato)copper(II) (complex 1), respectively. We found that the proliferation rate and viability of HL-60 cells decreased after treatment with complex 1, leading to cell death through apoptosis in a time-dependent manner. The antimicrobial activity of complex 1 has been tested, revealing an increased potency in comparison to the free Hpr-norf. Complex 1 proved to be capable of acting as an independent nuclease by inducing nicking of supercoiled pUC19 plasmid. Our results suggest that 1 may provide a valuable tool in cancer chemotherapy.
我们合成并表征了一种新型的氟喹诺酮类抗菌药物 N-丙基-诺氟沙星(Hpr-norf)与 1,10-菲咯啉(Phen)形成的铜(II)配合物,并研究了其作为抗肿瘤抗生素和抗菌剂的生物学特性。使用人急性髓性白血病细胞系 HL-60、MTT 法和台盼蓝法分别测试了(氯)(菲咯啉)(N-丙基-诺氟沙星基)铜(II)(配合物 1)的抗白血病作用、细胞活力、细胞膜的结构完整性以及细胞增殖特性。我们发现,用配合物 1 处理后,HL-60 细胞的增殖率和活力下降,导致细胞通过凋亡以时间依赖性方式死亡。测试了配合物 1 的抗菌活性,结果表明与游离的 Hpr-norf 相比其效力有所提高。配合物 1 被证明能够通过诱导超螺旋 pUC19 质粒的切口而作为一种独立的核酸酶起作用。我们的结果表明,配合物 1 可能为癌症化疗提供一种有价值的工具。