New copper(I) complexes bearing lomefloxacin motif: Spectroscopic properties, in vitro cytotoxicity and interactions with DNA and human serum albumin

• Published in: Journal of inorganic biochemistry 2016-12, Vol.165, p.25-35
• Main Authors: Komarnicka, Urszula K., Starosta, Radosław, Kyzioł, Agnieszka, Płotek, Michał, Puchalska, Małgorzata, Jeżowska-Bojczuk, Małgorzata
• Format: Article
• Language: English
• Subjects: Animals; Copper - chemistry; Copper - pharmacology; Copper(I) complexes; Cytotoxicity; Cytotoxins - chemical synthesis; Cytotoxins - chemistry; Cytotoxins - pharmacology; DNA - chemistry; DNA - metabolism; Female; Fluoroquinolones - chemical synthesis; Fluoroquinolones - chemistry; Fluoroquinolones - pharmacology; Humans; Lomefloxacin; Luminescence; MCF-7 Cells; Mice; Phosphines; Serum Albumin - chemistry; Spectrophotometry
• ISSN: 0162-0134; 1873-3344
• DOI: 10.1016/j.jinorgbio.2016.09.015

In this paper we present lomefloxacin's (HLm, 2nd generation fluoroquinolone antibiotic agent) organic and inorganic derivatives: aminomethyl(diphenyl)phosphine (PLm), its oxide as well as new copper(I) iodide or copper(I) thiocyanate complexes with PLm and 2,9-dimethyl-1,10-phenanthroline (dmp) or 2,2′-biquinoline (bq) as the auxiliary ligands. The synthesized compounds were fully characterised by NMR, UV–Vis and luminescence spectroscopies. Selected structures were analysed by theoretical DFT (density functional theory) methods. High stability of the complexes in aqueous solutions in the presence of atmosferic oxygen was proven. Cytotoxic activity of all compounds was tested towards three cancer cell lines (CT26 - mouse colon carcinoma, A549 - human lung adenocarcinoma, and MCF7 - human breast adenocarcinoma). All complexes are characterised by cytotoxic activity higher than the activity of the parent drug and its organic derivatives as well as cisplatin. Studied derivatives as well as parent drug do not intercalate to DNA, except Cu(I) complexes with bq ligand. All studied complexes caused single-stranded cleavage of the sugar–phosphate backbone of plasmid DNA. The addition of H2O2 caused distinct changes in the plasmid structure and led to single- and/or double-strain plasmid cleavage. Studied compounds interact with human serum albumin without affecting its secondary structure. Synopsis Herein we present lomefloxacin's derivative: aminomethyl(diphenyl)phosphine and its CuI or CuNCS complexes with diimine. High stability of the complexes in aqueous solutions in the presence of oxygen was proven. All complexes exhibit cytotoxicity (towards CT26, A549 MCF7 – cancer cell lines) higher than the toxicity of lomefloxacin and cisplatin. [Display omitted] •Phosphine derived from lomefloxacin and its Cu(I) complexes were synthesized.•All the compounds are stable and luminescent in solutions.•Compounds cytotoxicity was tested in vitro towards: CT26, A549 and MCF7 cell lines.•Studied complexes caused single-stranded cleavage of plasmid DNA.•Studied compounds interact with HSA without affecting its secondary structure.