Avaliação da atividade IMAO e antibacteriana de extratos de Mikania glomerata Sprengel

Neste trabalho avaliou-se a atividade antibacteriana e IMAO de extratos de diferentes polaridades de Mikania glomerata. A atividade antibacteriana foi medida frente à cepa multiresistente de Staphylococus aureus PI57, através das técnicas de bioautografia e antibiograma. A atividade IMAO foi medida utilizando uma suspensão de mitocôndrias. Mikania glomerata mostrou conter no extrato hexânico substâncias antimicrobianas. Os extratos hexânico e CH2Cl2 foram ativos frente à MAO-B, sem apresentarem atividade de inibição da MAO-A, enquanto o extrato metanólico apresentou atividade de inibição da MAO-A e MAO-B, sem seletividade.

Antibacterial and IMAO inhibition activities of different polarities extracts of Mikania glomerata were evaluated. The antibacterial activity was assayed against a multiresistant strain of Staphyllococus aureus PI57. The IMAO activity was measured with a suspension of mitochondrion. In the hexanic extract of Mikania glomerata substances with antibacterial activity were detected. Hexanic and CH2Cl2 extracts showed MAO-B inhibition activity while MAO-A inhibition activity was not detected. The methanolic extract showed non-selective inhibition activity of MAO-A and MAO-B.

In vitro biotransformation of the selective serotonin reuptake inhibitor citalopram, its enantiomers and demethylated metabolites by monoamine oxidase in rat and human brain preparations.

This study was conducted to identify enzyme systems eventually catalysing a local cerebral metabolism of citalopram, a widely used antidepressant of the selective serotonin reuptake inhibitor type. The metabolism of citalopram, of its enantiomers and demethylated metabolites was investigated in rat brain microsomes and in rat and human brain mitochondria. No cytochrome P-450 mediated transformation was observed in rat brain. By analysing H2O2 formation, monoamine oxidase A activity in rat brain mitochondria could be measured. In rat whole brain and in human frontal cortex, putamen, cerebellum and white matter of five brains monoamine oxidase activity was determined by the stereoselective measurement of the production of citalopram propionate. All substrates were metabolised by both forms of MAO, except in rat brain, where monoamine oxidase B activity could not be detected. Apparent Km and Vmax of S-citalopram biotransformation in human frontal cortex by monoamine oxidase B were found to be 266 microM and 6.0 pmol min(-1) mg(-1) protein and by monoamine oxidase A 856 microM and 6.4 pmol min(-1) mg(-1) protein, respectively. These Km values are in the same range as those for serotonin and dopamine metabolism by monoamine oxidases. Thus, the biotransformation of citalopram in the rat and human brain occurs mainly through monoamine oxidases and not, as in the liver, through cytochrome P-450.

Monoamine oxidase inhibitory activity of some Hypericum species native to South Brazil.

The total methanol crude extracts and petroleum ether, chloroform, and methanol fractions obtained from Hypericum species, H. caprifoliatum, H. carinatum, H. connatum, H. cordatum, H. myrianthum, H. piriai, H. polyanthemum and H. brasiliense, all native to South Brazil, were assayed for monoamine oxidase A (MAO A) and MAO B inhibitory activity in rat brain mitochondrial preparations at concentrations ranging from 1 to 20microg mL(-1). Three benzopyrans, HP1 (6-isobutyryl-5,7-dimethoxy-2,2-dimethylbenzopyran), HP2 (7-hydroxy-6-isobutyryl-5-methoxy-2,2-dimethylbenzopyran) and HP3 (5-hydroxy-6-isobutyryl-7-methoxy-2,2dimethylbenzopyran) isolated from H. polyanthemum were also tested at maximal concentrations of 150, 150 and 75/microM, respectively. The lipophilic extracts of H. polyanthemum, H. caprifoliatum and H. piriai displayed MAO A inhibitory activity greater than 50%. Among the benzopyrans, only HP3 showed significant activity, with an IC50 value of 22 microM. The total methanol crude extracts of aerial parts from H. carinatum, H. connatum, H. cordatum, H. polyanthemum and H. piriai were evaluated for antidepressant activity in the Porsolt's forced swimming test in Wistar rats (270 mg kg(-1) day(-1); i.p); however, none of them showed activity.

Interaction of psychotropic drugs with monoamine oxidase in rat brain.

Literature observations indicate that some psychotropic drugs may have inhibitory activity towards monoamine oxidase (MAO). This study was undertaken to assess the potency, isozyme selectivity and mechanism of inhibition of representative first- and second-generation antidepressant drugs towards rat brain MAO-A and MAO-B. Five tricyclic antidepressants (imipramine, trimipramine, clomipramine, amitriptyline and doxepine) and three selective serotonin reuptake inhibitors (fluoxetine, fluvoxamine and citalopram) were examined. They showed inhibitory activity towards MAO-A and MAO-B, with clear selectivity for MAO-B (Ki in the micromolar range). Their mechanism of inhibition was competitive towards MAO-B and of a mixed competitive type towards MAO-A. The results suggest that some of the drugs examined might also contribute an MAO inhibitory effect in chronically treated patients.

Inhibition of monoamine oxidases by functionalized coumarin derivatives: biological activities, QSARs, and 3D-QSARs.

A large series of coumarin derivatives (71 compounds) were tested for their monoamine oxidase A and B (MAO-A and MAO-B) inhibitory activity. Most of the compounds acted preferentially on MAO-B with IC(50) values in the micromolar to low-nanomolar range; high inhibitory activities toward MAO-A were also measured for sulfonic acid esters. The most active compound was 7-[(3, 4-difluorobenzyl)oxy]-3,4-dimethylcoumarin, with an IC(50) value toward MAO-B of 1.14 nM. A QSAR study of 7-X-benzyloxy meta-substituted 3,4-dimethylcoumarin derivatives acting on MAO-B yielded good statistical results (q(2)() = 0.72, r(2)() = 0.86), revealing the importance of lipophilic interactions in modulating the inhibition and excluding any dependence on electronic properties. CoMFA was performed on two data sets of MAO-A and MAO-B inhibitors. The GOLPE procedure, with variable selection criteria, was applied to improve the predictivity of the models and to facilitate the graphical interpretation of results.

Monoamine oxidase inhibitor properties of some benzazoles: structure-activity relationships.

Benzazoles containing two or three nitrogen atoms were screened for their inhibitory activity toward monoamine oxidases MAO-A and MAO-B. In order to clarify the mechanism of interaction of these compounds with the enzyme, their electronic structure was calculated at the ab initio level and the influence of lipophilicity on activity was investigated. The mode of binding of benzazoles to MAO-B appears different from that of previously investigated heterocycles.