title: Copper(I) (pseudo)halide complexes with neocuproine and aminomethylphosphines derived from morpholine and thiomorpholine - in vitro cytotoxic and antimicrobial activity and the interactions with DNA and serum albumins.
abstract: Herein, a series of CuI or CuNCS complexes with neocuproine (2,9-dimethyl-1,10-phenanthroline: dmp) and two tris(aminomethyl)phosphines derived from morpholine (P(CH2 N(CH2 CH2 )2 O)3 ) or thiomorpholine (P(CH2 N(CH2 CH2 )2 S)3 ) were tested as cytotoxic agents in vitro towards mouse colon carcinoma (CT26) and human lung adenocarcinoma (A549). The studies showed that the complexes exhibit potential antitumor properties, displayed by IC50 values below 10 μm towards the tested cell lines, in the case of 4-h incubation time with the examined compounds. Moreover, a high antimicrobial activity of all the complexes was observed against Staphylococcus aureus and Candida albicans with minimal inhibitory concentrations equal to 1-2 μg/mL. To gain insight into the molecular mechanism of biological activity of the complexes, we investigated also their interactions with plasmid DNA (pUC18) and the human and bovine serum albumins. Gel electrophoresis experiments demonstrated that all the compounds were comparably efficient in DNA degradation process; however, luminescence quenching showed surprising dependence on the interactions strength of the used compounds with the albumins. Apart from exceptionally effective [CuI(dmp)P(CH2 N(CH2 CH2 )2 O)3 ], the complexes with P(CH2 N(CH2 CH2 )2 O)3 quenched more strongly luminescence of bovine serum albumin, while the complexes with P(CH2 N(CH2 CH2 )2 S)3 were more active in the quenching of human serum albumin luminescence.
authors.affiliation: Faculty of Chemistry, University of Wrocław, ul. F. Joliot-Curie 14, 50-383, Wrocław, Poland.
authors.forename: Radosław
authors.initials: R
authors.lastname: Starosta
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Bykowska
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Kyzioł
authors.forename: Michał
authors.initials: M
authors.lastname: Płotek
authors.forename: Magdalena
authors.initials: M
authors.lastname: Florek
authors.forename: Jarosław
authors.initials: J
authors.lastname: Król
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Jeżowska-Bojczuk
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D002176:Candida albicans / Q000187:drug effects; D002417:Cattle; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D056831:Coordination Complexes / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D003300:Copper / Q000737:chemistry*; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008826:Microbial Sensitivity Tests; D009025:Morpholines / Q000737:chemistry; D010618:Phenanthrolines / Q000737:chemistry*; D010720:Phosphines / Q000737:chemistry*; D012709:Serum Albumin / Q000737:chemistry / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000187:drug effects
chemical_list: D000890:Anti-Infective Agents; D056831:Coordination Complexes; D009025:Morpholines; D010618:Phenanthrolines; D010720:Phosphines; D012709:Serum Albumin; C028971:thiamorpholine; D003300:Copper; C037574:morpholine; C002701:neocuproine; D004247:DNA
keywords: aminomethylphosphines; antibacterial and antifungal activity; copper(I) complexes; cytotoxic activity in vitro; human and bovine serum albumins; luminescence quenching; plasmid gel electrophoresis