The effect of verapamil on human flora bacteria, in vitro and in silico analysis of its interaction with DNA

Verapamil, a synthetic papaverine derivative, is widely used by millions of patients for treatment of high blood pressure and heart diseases in our country. Since antihypertensive drugs which are calcium channel blockers show chemical heterogeneity, they are the most discussed drug group in terms of side effects in recent years. In order to analyze Verapamile-DNA interaction the supercoiled plasmid DNA was treated with Verapamil and analyzed with agarose gel electrophoresis. This experiment was repeated in the presence of ascorbic acid, hydrogen peroxide, iron, iron plus hydrogen peroxide, copper, copper plus ascorbic acid. Verapamil-DNA interactions were investigated by UV-Vis spectrophotometer method and in silico analysis. The effect of the Verapamil on some human intestinal flora bacteria was investigated using broth medium dilution method and agar disc diffusion method. According to the results of agarose gel electrophoresis, Verapamil did not directly cause any damages on supercoiled plasmid DNA and it showed no protection effect against iron and copper mediated DNA damages. In the UV-Vis spectrophotometer analysis Verapamil did not show any interaction with the DNA. In contrast, in-silico analysis showed the drug to bind to ABSTRACT (continued) a minor groove of double helix DNA by 6 hydrogen bonds and hydrophobic interactions and binding energy value of -7.3. The drug inhibit the growth of both Enterococcus faecalis (gram positive strain) and Escherichia coli (gram negative strain) up to 90% at concentrations of 9, 18 and 25mM. 9mM of the drug was determined as both MIC and MBC value for the two bacterial strains.