Parkinson’s and Alzheimer’s diseases are neurodegenerative diseases that affect millions. There is currently no cure. These disorders are caused by reduced levels of numerous monoamines such as serotonin, dopamine, and norepinephrine, resulting in apoptosis and other forms of neurodegeneration. This project designed and prepared six phenothiazine derivatives as MAO-B inhibitors. In order to gain insights into the SARS between the inhibitors and MAO enzyme, the molecular docking simulations were preformed using Autodock Vina and Schrodinger Maestro software. The MAO crystal structure of safinamide (PDB ID: 2V5Z) was selected as the receptor. Safinamide was selected as the reference compound in the simulations. The enzymic reactions were studied by determining the amount of 4-hydroxyquinoline produced from kynuramine. Fluorescence measurements were conducted using a Varian Cary Eclipse Fluorescence Spectrophotometer. The experimental data show that the percent inhibition of the compounds is better than safinamide.

Synthesis of phenothiazine derivatives as MAO-B inhibitors for the treatment of neurodegenerative diseases

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ACS Fall 2022

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