Implementação de teste para a Monoamina oxidase B e atividade inibitória de composto indólicos em comparação com a acetilcolinesterase

Abstract

Neurodegenerative diseases such as Parkinson’s and Alzheimer’s are associated with neurotransmitter degradation and increased oxidative stress, processes mainly mediated by the enzymes monoamine oxidase B (MAO-B) and acetylcholinesterase (AChE). Selective inhibition of these enzymes is a promising strategy for the development of new neuroprotective drugs. This study aimed to implement a spectrophotometric assay for MAO-B evaluation and to investigate the inhibitory activity of nine indole chalcones synthesized through aldol condensation between 1H-indole-3-carbaldehyde and para-substituted ketones. Brain samples from Rattus norvegicus were used to obtain the enzymatic fraction, according to a protocol approved by the CEUA (No. 1.212/2022). MAO-B activity was determined following the method of Vinel et al. (2021), using benzylamine and DNPH as substrate and colorimetric reagent, respectively, while AChE inhibition was evaluated according to the Ellman method modified by Dingova et al. (2014). The results revealed greater selectivity of the chalcones toward MAO-B, with compounds 3c (p-F), 3f (p-OH), and 3g (p-OCH3) standing out, presenting IC50 values of 36.01 ± 10.5 µM, 47.81 ± 19.76 µM, and 69.74 ± 14.54 µM, respectively. For AChE, IC₅₀ values were higher than 230 µM. Therefore, indole chalcones exhibit significant selectivity for MAO-B, representing a promising class of inhibitors with potential palliative therapeutic applications for the treatment of neurodegenerative diseases.