title: Novel copper(II) complex of N-propyl-norfloxacin and 1,10-phenanthroline with enhanced antileukemic and DNA nuclease activities.
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.
authors.affiliation: Laboratory for Chemical Biology, Institute of Physical Chemistry, NCSR Demokritos, Paraskevi Attikis, Greece.
authors.forename: Maria E
authors.initials: ME
authors.lastname: Katsarou
authors.forename: Eleni K
authors.initials: EK
authors.lastname: Efthimiadou
authors.forename: George
authors.initials: G
authors.lastname: Psomas
authors.forename: Alexandra
authors.initials: A
authors.lastname: Karaliota
authors.forename: Dionisios
authors.initials: D
authors.lastname: Vourloumis
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003300:Copper; D004278:DNA, Superhelical / Q000378:metabolism*; D003851:Deoxyribonucleases / Q000378:metabolism*; D004926:Escherichia coli / Q000187:drug effects; D005434:Flow Cytometry; D018922:HL-60 Cells; D006801:Humans; D015470:Leukemia, Myeloid, Acute; D008826:Microbial Sensitivity Tests; D009336:Necrosis; D009643:Norfloxacin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010618:Phenanthrolines / Q000737:chemistry; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D013211:Staphylococcus aureus / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D004278:DNA, Superhelical; C528498:N-propylnorfloxacin; D009942:Organometallic Compounds; D010618:Phenanthrolines; C528497:chloro(1,10-phenanthroline)(N-propylnorfloxacinato)copper(II); D003300:Copper; D003851:Deoxyribonucleases; D009643:Norfloxacin; C025205:1,10-phenanthroline