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新型N-丙基-诺氟沙星与1,10-菲咯啉的铜(II)配合物,具有增强的抗白血病和DNA核酸酶活性。

Novel copper(II) complex of N-propyl-norfloxacin and 1,10-phenanthroline with enhanced antileukemic and DNA nuclease activities.

作者信息

Katsarou Maria E, Efthimiadou Eleni K, Psomas George, Karaliota Alexandra, Vourloumis Dionisios

机构信息

Laboratory for Chemical Biology, Institute of Physical Chemistry, NCSR Demokritos, Paraskevi Attikis, Greece.

出版信息

J Med Chem. 2008 Feb 14;51(3):470-8. doi: 10.1021/jm7013259. Epub 2008 Jan 19.

Abstract

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.

摘要

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。

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