Effect of Cd, Zn and Hg complexes of barbituric acid and thiouracil on rat brain monoamine oxidase-B (in vitro)

Abstract

Metal pyrimidine complexes (MPCs) including cadmium–barbiturate (Cd–BA), zinc–barbiturate (Zn–BA), cadmium–thiouracil (Cd–TU) and mercury–thiouracil (Hg–TU) were prepared and their analysis was carried out. These MPCs were evaluated as monoamine oxidase-B (MAO-B) inhibitors. Rat brain MAO-B was inhibited (in vitro) by Cd–BA, Zn–BA, Cd–TU and Hg–TU complexes. The inhibition of MAO-B by these complexes was time and concentration dependent. The values of IC50 of Zn–BA, Cd–BA, Hg–TU and Cd–TU were 10.2, 15.8, 16.2 and 20.4 nM, respectively. The effect of different substrate concentrations in the absence and in the presence of MPCs was determined. Lineweaver–Burk plots were plotted and the values of apparent Michaelis constant (Km), maximum velocity (Vmax), the dissociation constant of enzyme inhibitor complex (Ki) and the percent of inhibition (i%) were calculated. The data showed that the inhibition of MAO-B by all studied MPCs was the non-competitive type. The sequence of inhibition zone was: Zn–BA>Cd–BA and Hg–TU>Cd–TU affected by the chemistry of both the metal and the ligand. Otherwise, the results of the present study showed that the inhibition of MAO-B by all MPCs was fully reversible. The data showed that the presence of Cd–BA, Zn–BA, Cd–TU and Hg–TU complexes changed the optimum temperature and pH of MAO-B.