RESUMO
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.
Assuntos
Barbitúricos/farmacologia , Encéfalo/efeitos dos fármacos , Encéfalo/enzimologia , Metais Pesados/farmacologia , Monoaminoxidase/metabolismo , Tiouracila/farmacologia , Animais , Encéfalo/metabolismo , Cádmio/farmacologia , Interações Medicamentosas , Concentração de Íons de Hidrogênio , Masculino , Mercúrio/farmacologia , Inibidores da Monoaminoxidase/farmacologia , Ratos , Ratos Sprague-Dawley , Temperatura , Zinco/farmacologiaRESUMO
The effects of some pyrimidine compounds (PCs) including barbituric acid (BA) 5,5-diethyl barbituric acid (DEBA), 2-thiobarbituric acid (TBA), violuric acid (VA), 2-thiouracil (TU), and 6-amino-2-thiouracil (ATU) on the activity of rat brain monoamine oxidase-B (MAO-B) were investigated. The results revealed that MAO-B was activated by BA, DEBA, TBA, TU, and ATU, and the activation was structural, concentration, and time dependent. However, MAO-B was inhibited by VA in a noncompetitive and irreversible manner with an enzyme-inhibitor dissociation constant (K i value) of 32 nM and IC50 equals to 19 nM. All the studied PCs changed both the optimum pH and temperature of MAO-B (AU)
Assuntos
Animais , Ratos , Pirimidinas/farmacocinética , Cérebro , Monoaminoxidase , Tiouracila/farmacocinética , Barbitúricos/farmacocinéticaRESUMO
The effects of some pyrimidine compounds (PCs) including barbituric acid (BA) 5,5-diethyl barbituric acid (DEBA), 2-thiobarbituric acid (TBA), violuric acid (VA), 2-thiouracil (TU), and 6-amino-2-thiouracil (ATU) on the activity of rat brain monoamine oxidase-B (MAO-B) were investigated. The results revealed that MAO-B was activated by BA, DEBA, TBA, TU, and ATU, and the activation was structural, concentration, and time dependent. However, MAO-B was inhibited by VA in a noncompetitive and irreversible manner with an enzyme-inhibitor dissociation constant (K (i) value) of 32 nM and IC(50) equals to 19 nM. All the studied PCs changed both the optimum pH and temperature of MAO-B.
