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Amide Coupling Reaction for the Synthesis of Bispyridine-based Ligands and Their Complexation to Platinum as Dinuclear Anticancer Agents
Published on: May 28, 2014
Synthesis, characterization and DNA binding studies of a new ibuprofen-platinum(II) complex
Farshad Shiri1,2, Saba Hadidi3,4, Mehdi Rahimi-Nasrabadi1,2
1Chemical Injuries Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran.
Abstract:
The study is focused on the synthesis of a novel complex of ibuprofen and Platinum(II). The formation of the product was characterized through analytical tools including Fourier-transform infrared spectroscopy, proton nuclear magnetic resonance, ultraviolet-visible spectroscopy, mass spectrometry as well as density functional theory. Using the continuous variation method, the stoichiometry of Pt(HIb)2(Cl)2 binding on DNA (ct-DNA) determines as a single class of binding. Based on the results of Stern-Volmer analysis on the fluorescence quenching data, the quenching mechanism was determined to be static in nature. The studies indicated that the complex could bind DNA molecules via groove binding for four major reasons. Initially, the complex-DNA binding constant determined based on spectrophotometric data were found to be comparable to those of groove-binding drugs. In addition, the competitive fluorimetric based on the applications of Hoechst 33258 proved the ability of Pt(HIb)2(Cl)2 to displace with Hoechst in its DNA-bounded form, reflecting the competition between Pt(HIb)2(Cl)2 and Hoechst for groove binding. Further, no considerable changes were observed in the intensity of the methylene blue (MB)-DNA system after adding the Pt(HIb)2(Cl)2 complex, reflecting the stability of MB molecules in the DNA helix and a non-intercalative bonds of Pt(HIb)2(Cl)2 interaction on DNA. Finally, minor changes in the viscosity of DNA in the presence of Pt(HIb)2(Cl)2, indicated that changes in the length of DNA in the presence of the complex are negligible, supporting the assumption of DNA groove-binding. Also induced CD spectral changes and docking simulations were in favor of the groove mechanism for the Pt(HIb)2(Cl)2-DNA binding.Communicated by Ramaswamy H. Sarma.
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