In vitro and in silico analysis of the effect of fluconazole, an antifungal drug, on DNA

Abstract

Fluconazole is an important antifungal drug used worldwide for the treatment of peritonitis and cryptococcal meningitis, urinary tract infections, esophageal tract infections and vaginal candidiasis. In this research, pUC19 plasmid DNA was treated with different concentrations of fluconazole in the presence of ascorbic acid, H2O2, iron, iron plus H2O2, copper and copper plus ascorbic acid, followed by agarose gel electrophoresis. Fluconazole–DNA interactions were investigated by UV–Vis spectrophotometeric titration and in silico methods. Even in the presence of an oxidative agent or a reducing agent, at higher concentrations of fluconazole, double stranded DNA was not broken more than usually found in human plasma. Fluconazole concentrations ≥ 88 μM could protect 46 µM of DNA against hydroxyl radicals produced in the reaction between 1.5 mM of FeSO4 and 6 mM of H2O2 while drug concen­trations ≤ 44 μM could not provide the protection. In addition, the drug could not protect DNA against ROS originating from the reaction between copper and ascorbic acid. The binding constant of fluconazole–DNA in UV-Vis spec­trophotometry analysis and docking analysis was estimated to be 1.087×103 and 6.22×105 M-1, respectively.