Synthesis, in vitro enzyme activity and molecular docking studies of new benzylamine-sulfonamide derivatives as selective MAO-B inhibitors

Abstract

Many studies have been conducted on the selective inhibition of human monoamine oxidase B ( h MAO-B) enzyme using benzylamine-sulphonamide derivatives. Using various chemical modifications on BB-4h , which was reported previously by our team and showed a significant level of MAO-B inhibition, novel benzylamine-sulphonamide derivatives were designed, synthesised, and their MAO inhibition potentials were evaluated. Among the tested derivatives, compounds 4i and 4t achieved IC 50 values of 0.041 ± 0.001 µM and 0.065 ± 0.002 µM, respectively. The mechanism of h MAO-B inhibition by compounds 4i and 4t was studied using Lineweaver–Burk plot. The nature of inhibition was also determined to be non-competitive. Cytotoxicity tests were conducted and compounds 4i and 4t were found to be non-toxic. Molecular docking studies were also carried out for compound 4i , which was found as the most potent agent, within h MAO-B catalytic site.

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“…It is worthwhile to note that the inhibition of the h MAOs not only causes an increasing amount of the monoamine neurotransmitters but also causes decreases in the levels of hydrogen peroxide (H 2 O 2 ) and hydroxyl radicals, which are responsible for the elevated level of reactive oxygen species (ROS) . The h MAO-A and h MAO-B isoenzymes are encoded by distinct genes on the X chromosome, and they have nearly 70% sequence identity . Although the h MAO-A inhibitors have been used in the therapy of depression, anxiety and other affective disorders, the h MAO-B inhibitors have been preferred in some neurodegenerative diseases (NDs) such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), and amyotrophic lateral sclerosis (ALS) .…”

Recent updates on structural insights of MAO-B inhibitors: a review on target-based approach

“…Cytotoxicity assay was performed against the NIH3T3 cell line and found that compounds 11 and 12 showed an IC 50 value of greater than 1000 which is significantly higher than the effective concentration, and it can be concluded that these compounds were non-cytotoxic at their effective concentration. Molecular docking studies were performed for compound 11, and found that it has a good binding affinity with the MAO-B enzyme [ 92 ].

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Synthesis and characterization of new Piperazine-Dithiocarbamate compounds as potent MAO-A inhibitors

“…The in vitro MAO inhibition test was carried out using the standard fluorometric method, and the percentages and IC 50 values of the compounds obtained were reported as described by our research group already [19][20][21][22][23][24][25].…”