In this paper, three new copper (II) complexes, [Cu(4-mphen)(tyr)(H 2 O)] ClO 4 (1), [Cu(5-mphen)(tyr)(H 2 O)]ClO 4 ·1.5H 2 O (2) and [Cu (tmphen)(tyr) (NO 3 )]0.5H 2 O (3) (4-mphen: 4-methyl-1,10-phenanthroline, 5-mphen: 5-methyl-1,10-phenanthroline, tmphen: 3,4,7,8-tetramethyl-1,10-phenanthroline and tyr: L-tyrosine), were synthesized and characterized using elemental analyses, FT-IR, ESI-MS, cyclic voltammetry and single-crystal X-ray diffraction. It was found that the complexes adopt a distorted five-coordinate square pyramidal geometry. The interaction of the three complexes with calf thymus DNA was also investigated using UV-visible absorption spectra, ethidium bromide and Hoechst 33258 displacement assay and thermal denaturation. The DNA cleavage activity of the complexes, monitored using gel electrophoresis, showed significant damage of the pUC19 plasmid DNA. Binding activity of bovine serum albumin (BSA) reveals that these complexes can strongly quench the fluorescence of BSA through a static quenching mechanism. The results suggested that interaction of the complexes with DNA occurred through a partial intercalation into the minor grooves of DNA. In addition, interaction of the complexes with bovine serum albumin quenched the fluorescence emission of the tryptophan residues of the protein binding constants and thermodynamic parameters were obtained from the fluorescence quenching experiments at different temperatures. Free radical scavenging activities of the complexes were determined by various in vitro assays such as 1,1-diphenyl-2-picryl-hydrazyl free radicals (DPPH˙) and H 2 O 2 scavenging methods. In addition, the cytotoxicity of these complexes in vitro on tumor cell lines (Caco-2 and MCF-7) was examined by XTT and showed better antitumor effect on the tested cells. ROS (reactive oxygen species) and comet experiments are consistent with each other and these complexes lead to DNA damage via the production of ROS. The effect of the hydrophobic properties of the synthesized complexes on DNA and BSA binding activities were discussed.

Three novel water‐soluble copper(II) complexes – {[Cu(phen)(trp)]ClO4·3H2O}n (1), {[Cu(4‐mphen)(trp)]ClO4·3H2O}n (2) and [[Cu(dmphen)(trp)(MeOH)][Cu(dmphen)(trp)(NO3)]]NO3 (3) (phen: 1,10‐phenanthroline; 4‐mphen: 4‐methyl‐1,10‐phenanthroline; dmphen: 4,7‐dimethyl‐1,10‐phenanthroline; trp: l‐tryptophan) – have been synthesized and characterized using various techniques. Complexes 1 and 2 are isostructural, and exist as one‐dimensional coordination polymers. Complex 3 consists of two discrete copper(II) complexes containing [Cu(trp)(dmphen)(MeOH)]+, [Cu(trp)(dmphen)(NO3)] and one nitrate anion. The binding interaction of the complexes with calf thymus DNA (CT‐DNA) was investigated using thermal denaturation, electronic absorption and emission spectroscopic methods, revealing that the complexes could interact with CT‐DNA via a moderate intercalation mode. The binding activity of the complexes to CT‐DNA follows the order: 3 > 2 > 1. The pUC19 DNA cleavage activity of the complexes was investigated in the absence and presence of external agents using the agarose gel electrophoresis method. Especially, in the presence of H2O2 as an activator, the pUC19 DNA cleavage abilities of the complexes are clearly enhanced at low concentration. Addition of hydroxyl radical scavenger dimethylsulfoxide shows a marked inhibition of the pUC19 DNA cleavage activity of the complexes. In vitro cytotoxic effect of the complexes was examined on human tumor cell lines (Caco‐2, A549 and MCF‐7) and healthy cells (BEAS‐2B). The potent cytotoxic effect of complex 3, with IC50 values of 1.04, 1.16 and 1.72 μM, respectively, is greater relative to clinically used cisplatin (IC50 = 22.70, 31.1 and 22.2 μM) against the Caco‐2, A549 and MCF‐7 cell lines.

pyrazino[2,3-f][1,10]phenanthroline; gly: glycine;tyr: tyrosine), have been synthesized and characterized using CHN analysis, electrospray ionization mass spectrometry, Fourier transform infrared spectroscopy and single-crystal X-ray diffraction. Interaction of these complexes with calf thymus DNA has been investigated using absorption spectral titration, ethidium bromide and Hoechst 33258 displacement assay and thermal denaturation measurements. These complexes were found to be efficient cleaving agents and cleavage reactions were mediated by hydrolytic and oxidative pathways. The interaction between these complexes and bovine serum albumin (BSA) was investigated using electronic absorption and fluorescence spectroscopy. The experimental results show that the fluorescence quenching mechanism of these complexes and BSA is a static quenching process. Furthermore, in vitro cytotoxicities of these complexes against tumour cell lines (Caco-2, MCF-7 and A549) and healthy cell line (BEAS-2B) showed that they exhibited anticancer activity with low IC 50 values. These complexes were markedly active against the cell lines and can be good drug candidates that are effective and safe for healthy tissue.

In vitro cytotoxic and genotoxic effects of donkey milk on cancer (A549) and normal (BEAS-2B) lung cell lines were investigated. The XTT and WST-1 tests as well as clonogenic assays were used to evaluate cytotoxicity. The comet assay and micronucleus test were used as genotoxicity endpoints. Donkey milk showed lower cytotoxic effects against normal lung cell line BEAS-2B in comparison to the tumor cell line A549. Genotoxicity experiments revealed dose dependent increases in the frequencies of micronuclei and single stranded DNA breaks in A549 cells whereas no significant damage was observed in BEAS-2B cells. The results indicate that donkey milk has anti-proliferative and genotoxic effects on lung cancer cells at concentrations which are non-toxic to normal lung cells.

STAT3 plays an important role in various complex and sometimes contradictory pathways such as proliferation, differentiation, migration, inflammation, and apoptosis. The transcriptional activity of the STAT3 gene is controlled by a transcription factor called ZNF341. There is insufficient data on radiation sensitivity and post-radiation DNA repair in STAT3- loss-of-function (LOF) patients. We aimed to investigate the radiosensitivity in patients with STAT3-LOF and ZNF341 deficiency. Twelve patients with STAT3-LOF and four ZNF341-deficiency patients were recruited from three clinical immunology centers in Turkey and evaluated for radiosensitivity by the Comet assay, comparing to 14 age- and sex-matched healthy controls. The Tail length (μm), Tail DNA (%), Olive Tail Moment (OTM) (arbitrary units) were evaluated at the same time for baseline (spontaneous), initial (immediately after 2Gy irradiation), and recovery (2h after irradiation) periods by using a computerized image-analysis system, estimating DNA damage. Except for a patient with ZNF341 deficiency who developed nasal cell primitive neuroendocrine tumor and papillary thyroid cancer during the follow-up, there was no cancer in both groups. During the recovery period of irradiation, TL, TDNA%, and OTM values of healthy controls decreased rapidly towards the baseline, while these values of patients with STAT3-LOF and ZNF341 deficiency continued to increase, implying impaired DNA repair mechanisms. Increased radiosensitivity and impaired DNA repair were demonstrated in patients diagnosed with STAT3-LOF and ZNF341 deficiency, potentially explaining the susceptibility to malignant transformation.