New binary copper(II) complexes containing intercalating ligands: DNA interactions, an unusual static quenching mechanism of BSA and cytotoxic activities


Inci D. , Aydin R., Vatan O., Zorlu Y., Cinkilic N.

JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS, cilt.36, ss.3878-3901, 2018 (SCI İndekslerine Giren Dergi) identifier identifier identifier

  • Cilt numarası: 36 Konu: 15
  • Basım Tarihi: 2018
  • Doi Numarası: 10.1080/07391102.2017.1404936
  • Dergi Adı: JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
  • Sayfa Sayıları: ss.3878-3901

Özet

New binary copper(II) complexes - [Cu(4-mphen)(2)(NO3)]NO3 center dot H2O (1), [Cu(5-mphen)(2) (NO3)]NO3 center dot H2O (2), the known complex [Cu(dmphen)(2)(NO3)]NO3 (3) and [Cu(tmphen)(2) (NO3)]NO3 center dot H2O (4) - (4-mphen: 4-methyl-1,10-phenanthroline, 5-mphen: 5-methyl-1,10-phenanthroline, dmphen: 4,7-dimethyl-1,10-phenanthroline, tmphen: 3,4,7,8-tetramethyl-1,10-phenanthroline), have been synthesized and characterized by CHN analysis, ESI-MS, FTIR and single-crystal X-ray diffraction techniques. Interaction of these complexes with calf thymus DNA (CT-DNA) has been investigated by absorption spectral titration, ethidium bromide (EB) and Hoechst 33,258 displacement assay and thermal denaturation measurement. These complexes cleaved pUC19 plasmid DNA in the absence and presence of an external agent. Notably, in the presence of H2O2 as an activator, the cleavage abilities of these complexes are obviously enhanced at low concentration. Addition of hydroxyl radical scavengers like DMSO shows significant inhibition of the DNA cleavage activity of these complexes. BSA quenching mechanism was investigated with regard to the type of quenching, binding constant, number of binding locations and the thermodynamic parameters. The experimental results suggested that the probable quenching mechanism was an unusual static process and hydrophobic forces play a dominant role. The CT-DNA and BSA binding efficiencies of these complexes follow the order: 4 > 3 > 1 > 2. Furthermore, in vitro cytotoxicities of these complexes on tumor cells lines (Caco-2, MCF-7 and A549) and healthy cell line (BEAS-2B) showed that these complexes exhibited anticancer activity with low IC50 values. The effect of hydrophobicity of the methyl-substituted phenanthrolines on DNA and protein binding activities of these complexes is discussed.