Rybakova K. Mechanisms of interaction of antibacterial drug Norfloxacin with DNA-binding aromatic ligands in aqueous solution

The aim of this work: forming a view about existence at molecular level of regulation mechanism of biological activity at the combined use of norfloxacin (NOR) with aromatic BACs. Methods of research are 1D and 2D NMR-spectroscopy and molecular modelling. A calculation and analysis of structural and thermodynamical parameters of NOR self-association and its hetero-association with studied BACs was made for the first time. Components of Gibb's free energy of the hetero-association reactions have been calculated. Complexation of NOR with DNA fragments 5'-d(TpGpCpA) and 5'-d(CpGpCpG) has been investigated, thermodynamical parameters and specificity of the binding with single- and double-stranded forms were determined. The process of competitive binding of BACs with DNA in three-component systems NOR-BАС-DNA has been investigated, the correlation of effektiveness of interceptor and protector mechanisms of action has been calculated, the estimation of relative change of biological effect was made. The threshold concentrations of aromatic BACs at which the effect of change of biological activity in the case of their combination in a dose with NOR have been determined. Field of application - molecular biophysics and biology.