Polymeric micelle-mediated delivery of half-sandwich ruthenium(II) complexes with phosphanes derived from fluoroloquinolones for lung adenocarcinoma treatment.

Novel half-sandwich ruthenium(II) complexes with aminomethyl(diphenyl)phosphine derived from fluoroloquinolones (RuPCp, RuPSf, RuPLm, RuPNr) were being investigated as alternatives to well-established metal-based chemotherapeutics. All compounds were characterized by elemental analysis, selected spectroscopic methods (i.e., absorption and fluorescence spectroscopies, ESI-MS, NMR, circular dichroizm), X-ray diffractometry, ICP-MS, and electrochemical techniques. To overcome low solubility, serious side effects connected with systemic cytotoxicity of ruthenium complexes, and acquiring the resistance of cancer cells, polymeric nanoformulations based on Pluronic P-123 micelles loaded with selected Ru(II) complexes were prepared and characterized. Resulting micelles (RuPCp_M, RuPNr_M) enabled efficient drug accumulation inside human lung adenocarcinoma (A549 tumor cell line), proved by confocal microscopy and ICP-MS analysis, allowing cytotoxic action. Studied complexes exhibited promising cytotoxicity in vitro with IC50 values significantly lower than the reference drug - cisplatin. The fluorescence spectroscopic data (CT-DNA titration, in vitro cell staining) together with analysis of DNA fragmentation (pBR322 plasmid, comet assay) provided clear evidence for the interaction with DNA inducing apoptotic cell death.

Ruthenium(II) piano stool coordination compounds with aminomethylphosphanes: Synthesis, characterisation and preliminary biological study in vitro.

Reaction of {[Ru(η6-p-cymene)Cl]2(µ-Cl)2} (1) with aminomethylphosphane derived from morpholine (P{CH2N(CH2CH2)2O}3 (A), PPh2{CH2N(CH2CH2)2O} (B)) or piperazine (P{CH2N(CH2CH2)2NCH2CH3}3 (C), PPh2{CH2N(CH2CH2)2NCH2CH3} (D)) results in four new piano stool ruthenium(II) coordination compounds: [Ru(η6-p-cymene)Cl2(A)] (2A), [Ru(η6-p-cymene)Cl2(B)] (2B), [Ru(η6-p-cymene)Cl2(C)] (2C) and [Ru(η6-p-cymene)Cl2(D)] (2D). Every complex was fully characterized using spectroscopic methods (1H, 13C{1H}, 31P{1H} NMR and ESI-MS), elemental analysis, X-ray single crystal diffraction and DFT calculations. Preliminary studies of in vitro cytotoxicity on the A549 (human lung adenocarcinoma) and MCF7 (human breast adenocarcinoma) cell lines revealed 2A-2D activity in the same order of magnitude as in the case of cisplatin. Additionally, the study confirmed the ability of 2A-2D to interact with DNA helix and transferrin.

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

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.

New ruthenium(II) coordination compounds possessing bidentate aminomethylphosphane ligands: synthesis, characterization and preliminary biological study in vitro.

Addition of aminomethylphosphane P{CH2N(CH2CH2)2O}3 (), PPh2{CH2N(CH2CH2)2O} () or PPh2{CH2N(CH2CH2)2NCH2CH3} () to a methanolic solution of RuCl3 results in reduction of ruthenium(iii) ions giving finally ttt-[RuCl2()2] (), ttt-[RuCl2()2] () and ttt-[RuCl2()2] (). The synthesized complexes are the first examples of ruthenium(ii) coordination compounds possessing aminomethylphosphanes chelating via phosphorus and nitrogen atoms. They were fully characterized (NMR, ESI-MS, IR, elemental analysis, X-ray crystallography). Preliminary studies of the in vitro cytotoxicity on the A549 cell line (human lung adenocarcinoma) and interactions with human serum proteins (albumin and apotransferrin) showed moderate activity of the complexes. Interestingly, the P,N-chelation leads to formation of strained 4-membered Ru-P-C-N-Ru rings, which in the case of and undergo opening in the presence of CH3CN, which results in rearrangement to ctc-[RuCl2()2(CH3CN)2] () and ctc-[RuCl2()2(CH3CN)2] ().

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.

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.