Enantiomeric Specificity of Biologically Significant Cu(II) and Zn(II) Chromone Complexes Towards DNA

Novel chiral Schiff base ligands (R)/(S)-2-amino-3-(((1-hydroxypropan-2-yl)imino) methyl)-4H-chromen-4-one (L-1 and L-2) derived from 2-amino-3-formylchromone and (R/S)-2-amino-1-propanol and their Cu(II)/Zn(II) complexes (R1, S1, R2, and S2) were synthesized. The complexes were characterized by elemental analysis, infrared (IR), hydrogen (H-1) and carbon (C-13) nuclear magnetic resonance (NMR), electrospray ionization-mass spectra (ESI-MS), and molar conductance measurements. The DNA binding studies of the complexes with calf thymus were carried out by employing different biophysical methods and molecular docking studies that revealed that complexes R1 and S1 prefers the guanine-cytosine-rich region, whereas R2 and S2 prefers the adenine-thymine residues in the major groove of DNA. The relative trend in K-b values followed the order R1>S1>R2>S2. This observation together with the findings of circular dichroic and fluorescence studies revealed maximal potential of (R)-enantiomeric form of complexes to bind DNA. Furthermore, the absorption studies with mononucleotides were also monitored to examine the base-specific interactions of the complexes that revealed a higher propensity of Cu(II) complexes for guanosine-50-monophosphate disodium salt, whereas Zn(II) complexes preferentially bind to thymidine-50-monophosphate disodium salt. The cleavage activity of R1 and R2 with pBR322 plasmid DNA was examined by gel electrophoresis that revealed that they are good DNA cleavage agents; nevertheless, R1 proved to show better DNA cleavage ability. Topoisomerase II inhibitory activity of complex R1 revealed that the complex inhibits topoisomerase II catalytic activity at a very low concentration (25 mu M). Furthermore, in vitro antitumor activity of complexes R1 and S1 were screened against human carcinoma cell lines of different histological origin. Chirality 24: 977-986, 2012. (C) 2012 Wiley Periodicals, Inc.