EXPLORATION OF PYRAZOLINE AND AMINO CHALCONE DERIVATIVES AS MONOAMINE OXIDASE INHIBITORS: AN IN-SILICO APPROACH

Abstract

Monoamine oxidase (MAO) is an enzyme involved in neurotransmitter monoamine metabolism through an oxidative deamination reaction that produces a nerve-damaging substance, H2O2. Two isoforms of MAO that are MAO-A, and MAO-B, are known by their specific substrates, serotonin, and dopamine, respectively. Overexpression of MAO-A causes depression and anxiety disorder, whereas MAO-B causes neurodegenerative disorders such as Parkinson’s and Alzheimer’s. Infections and diseases caused by the activity of these two enzymes are known to affect millions of people worldwide every year. Various drugs for both disorders are available on the market. However, side effects such as dizziness, sore throat, insomnia, obesity, and heart disorder are registered. Therefore, developing new compounds acting as MAO inhibitors with lower side effects but higher selectivity than available drugs is in need. Pyrazolines and amino chalcone derivatives are well known to exhibit inhibition of MAO activity and used as research objects. Virtual screening of molecular docking using DOCK6 of six compounds of each pyrazoline (1a-f) (both R and S configuration) and amino chalcone (2a-f) was conducted to study their inhibition activity to MAO-A (PDB: 2Z5X) and MAO-B (PDB: 6FW0) and selectivity based on comparison of grid score value of Harmin as control positive for MAO-A and E92 ligand for MAO-B. The results showed that the most potent compound as a selective inhibitor of MAO is (R)-3-(4-aminophenyl)-5-phenyl-4,5-dihydro-1H-pyrazole-1-carboxamide of pyrazoline derivative and (1- (4-cinnamoyl phenyl) thiourea) of amino chalcone derivative.