Investigation of the effect of fluconazole on flora bacteria, in vitro and in silico analysis of its binding to DNA

Fluconazole is widely used as an antifungal drug worldwide, especially in our country. Although there are some studies about the toxic effects of the drug, according to our study, there is no study about the fluconazole-DNA interactions and its antibacterial effect. In this study, oxidative and anti-oxidative effects of fluconazole, fluconazole-DNA interaction were investigated using UV-Vis spectrophotometer, agarose gel electrophoresis and in-silico method. In addition, effect of the drug on some human flora bacterial strains were studied by disc diffusion and broth dilution methods. The drug showed some protective effect on supercoiled plasmid DNA against breaking effect of hydroxyl radicals, while it did not exhibited any effect on the DNA at presence of iron, cupper, cupper plus ascorbic acid and ascorbic acid. In the analysis of the fluconazole-DNA interaction by UV Titration method, the increase in absorbance indicated that the compound had some interactions with the DNA. In this method binding constant of the drug with DNA was obtained as 179 M-1. In-silico analysis confirmed the result of UV Titration method by showing the bonding of the drug on a minor groove of double helix DNA by the binding energy of -3.09, making 3 hydrogen bonds and hydrophobic bonds. 24 mM of the drug inhibited the growth of Enterococcus faecalis, Proteus mirabilis, Enterobacter cloacae and Escherichia coli strains as 35%, 22%, 20% and 20% respectively.