The catechol-O-methyltransferase inhibitory potential of Z-vallesiachotamine by in silico and in vitro approaches

摘要: Z-Vallesiachotamine is a monoterpene indole alkaloid that has β-N-acrylate group in its structure. This class of compounds already been described different Psychotriaspecies. Our research observed E/Z-vallesiachotamine exhibits multifunctional feature, being able to inhibit targets related neurodegeneration, such as monoamine oxidase A, sirtuins 1 and 2, butyrylcholinesterase enzymes. Aiming at better characterizing the profile this compound, effect on cathecol-O-methyltransferase activity was investigated. The evaluated vitro by fluorescence-based method, using S-(5′-adenosyl)-l-methionine methyl donor aesculetin substrate. assay optimization performed varying concentrations (S-(5′-adenosyl)-l-methionine) enzyme. It highest both factors (2.25 U enzyme 100 µM S-(5′-adenosyl)-l-methionine) afforded more reproducible results. demonstrated Z-vallesiachotamine with an IC50 close 200 µM. Molecular docking studies indicated can bind catechol pocket catechol-O-methyltransferase present work for first time inhibitory properties enzyme, affording additional evidence regarding effects neurodegenerative diseases.