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 ((1) H) and carbon ((13)C) 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 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-5'-monophosphate disodium salt, whereas Zn(II) complexes preferentially bind to thymidine-5'-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 µM). Furthermore, in vitro antitumor activity of complexes R1 and S1 were screened against human carcinoma cell lines of different histological origin.

Synthesis, DNA recognition and cleavage studies of novel tetrapeptide complexes, Cu(II)/Zn(II)-Ala-Pro-Ala-Pro.

New tetrapeptide complexes Cu(II)·Ala-Pro-Ala-Pro (1) and Zn(II)·Ala-Pro-Ala-Pro (2) were synthesized from the reaction of tetrapeptide, Ala-Pro-Ala-Pro and CuCl2/ZnCl2 and were thoroughly characterized by elemental analysis, IR,(1)H and (13)C NMR (in case of 2), ESI-MS, UV and molar conductance measurements. The solution stability study was carried out employing UV-vis absorption titrations over a broad range of pH which suggested the stability of the complexes in solution. In vitro interaction of complexes 1 and 2 with CT-DNA was studied employing UV-vis, fluorescence, circular dichroic and viscometry studies. To throw insight into molecular binding event at the target site, UV-vis titrations of 1 and 2 with mononucleotides of interest viz.; 5'-GMP and 5'-TMP were carried out. Cleavage activity of the complexes with pBR322 plasmid DNA was evaluated by agarose gel electrophoresis and, the electrophoresis pattern demonstrated that both the complexes 1 and 2 are efficient cleavage agents. Further, the Cu(II) complex displayed efficient oxidative cleavage of supercoiled DNA while various reactive oxygen species are responsible for the cleavage in Zn(II) complex.

Synthesis, characterization and in vitro DNA binding and cleavage studies of Cu(II)/Zn(II) dipeptide complexes.

Novel dipeptide complexes Cu(II)-Val-Pro (1), Zn(II)-Val-Pro (2), Cu(II)-Ala-Pro (3) and Zn(II)-Ala-Pro (4) were synthesized and thoroughly characterized using different spectroscopic techniques including elemental analyses, IR, NMR, ESI-MS and molar conductance measurements. The solution stability study carried out by UV-vis absorption titration over a broad range of pH proved the stability of the complexes in solution. In vitro DNA binding studies of complexes 1-4 carried out employing absorption, fluorescence, circular dichroism and viscometric studies revealed the binding of complexes to DNA via groove binding. UV-vis titrations of 1-4 with mononucleotides of interest viz., 5'-GMP and 5'-TMP were also carried out. The DNA cleavage activity of the complexes 1 and 2 were ascertained by gel electrophoresis assay which revealed that the complexes are good DNA cleavage agents and the cleavage mechanism involved a hydrolytic pathway. Furthermore, in vitro antitumor activity of complex 1 was screened against human cancer cell lines of different histological origin.

DNA binding studies of new valine derived chiral complexes of tin(IV) and zirconium(IV).

Valine derived chiral complexes of SnCl4 (1) and ZrCl4 (2) were designed as potent antitumor agents. These complexes were characterized by elemental analysis, IR, 1H NMR, 119Sn NMR and ESI mass spectroscopy. In vitro binding studies of complexes 1 and 2 under physiological conditions at room temperature with CT-DNA were carried out employing UV-vis absorption titration, fluorescence studies and viscosity measurements. The extent of binding was quantified by Kb values of complexes 1 and 2 which were found to be 1.97×10(4) and 1.17×10(3) M(-1), respectively, suggesting that complex 1 has significantly greater DNA binding propensity in contrast to the complex 2. The mode of action at the molecular level was ascertained by the interaction of complex 1 with 5'GMP and 5'TMP which revealed that complex 1 binds via electrostatic mode with the oxygen of the negatively charged surface phosphate group of the DNA helix. The supercoiled pBR322 plasmid DNA cleavage activity of complex 1 was ascertained by gel electrophoresis assay.