| Texto completo | |
| Autor(es): |
Dos Reis, Vitor Eduardo Narciso
;
Franco, Graziella Dos Reis Rosa
;
de Souza, Mikaela Lucinda
;
da Silva, Matheus Muller Pereira
;
Guedes, Isabella Alvim
;
Dardenne, Laurent Emmanuel
;
Viegas Jr, Claudio
;
Cardoso, Carmen Lucia
Número total de Autores: 8
|
| Tipo de documento: | Artigo Científico |
| Fonte: | Journal of Pharmaceutical and Biomedical Analysis; v. 268, p. 8-pg., 2025-10-17. |
| Resumo | |
Monoamine oxidase A (MAO-A) and B (MAO-B) are critical enzymes involved in regulating neurotransmitters such as dopamine, serotonin, and norepinephrine. Dysregulated MAO activity is associated with neurological disorders, including Parkinson's disease, depression, and cardiovascular diseases, making MAO-A and MAO-B important therapeutic targets. Here, we present a novel assay using MAOs immobilized on magnetic beads (MB) in an immobilized enzyme reactor configuration (MAO-MB) to screen for selective MAO-A and MAO-B inhibitors. The immobilization of both enzymes proved efficient, as no protein was detected in the supernatant after the process by the Bradford assay. Enzyme activity was quantified using HPLC-MS, and kinetic parameters were evaluated, with apparent Michaelis-Menten constants (Kmapp) of 19.36 f 0.71 mu M for MAO-A-MB and 38.85 f 1.70 mu M for MAO-B-MB. The assay was qualified with toloxatone and safinamide as reference inhibitors, yielding IC50 values of 3.42 f 0.11 mu M and 33.38 f 1.38 nM, respectively. Additionally, a collection of terpenyl-benzohydrazides was screened, identifying PQM-244 (5c) as a selective MAO-B inhibitor (IC50 = 4.17 f 0.082 mu M) with a non-competitive inhibition mechanism (Ki = 2.28 f 0.38 mu M). These findings suggest that 5c (PQM-244) has significant potential to contribute to developing selective MAO-B inhibitors for Parkinson's disease therapy. (AU) | |
| Processo FAPESP: | 14/50299-5 - EMU - espectrômetro de massas modelo Amazon speed com fonte ESI e duplo funil de íons, analisador tipo íon TRAP |
| Beneficiário: | Quezia Bezerra Cass |
| Modalidade de apoio: | Auxílio à Pesquisa - Programa Equipamentos Multiusuários |