Abstract
Disulfiram (C10H20N2S4) is an acetaldehyde dehydrogenase inhibitor used in the treatment of chronic alcoholism and it has also been subjected to the clinical trial for cancer in recent times. However, there is no report on the binding effect of this emerging drug with DNA. Hence, the present investigation was taken up to study the binding effect of disulfiram on DNA under physiological conditions. UV–vis absorption spectroscopy, fluorescence emission spectroscopy, circular dichroism spectroscopy, cyclic voltammetry and molecular docking techniques were employed to determine the interaction mode of disulfiram with DNA. Further, DNA cleavage property of disulfiram was carried out by using agarose gel electrophoresis. The UV–vis absorption, emission and cyclic voltammetry measurements revealed that disulfiram showed the intercalative mode of interaction with DNA. The circular dichroism study exhibited structural changes of partial transition from B-conformation to A-conformation in DNA upon addition of disulfiram. Molecular docking study of disulfiram with DNA depicted intercalative mode of binding by formation of hydrogen and hydrophobic interaction along with docking score of −3.07kcal/mol. The DNA cleavage study revealed that low concentration of disulfiram (50µM) protected the DNA from oxidative damage sequentially, while high concentration of disulfiram (100µM) showed less protective activity. Conversely, it caused DNA damage in the presence of hydroxyl radical oxidative system. Hence, the results obtained from the present investigations provide detailed discernment into DNA interaction effects of disulfiram.
Published Version
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