Related Experiment Video
Updated: Feb 6, 2026

A Plate-Based Assay for the Measurement of Endogenous Monoamine Release in Acute Brain Slices
Published on: August 11, 2021
Curcumin-based pyrazoline analogues as selective inhibitors of human monoamine oxidase A
Chandrani Nath1, Vishnu Nayak Badavath1, Abhishek Thakur2
1Department of Pharmaceutical Sciences & Technology , Birla Institute of Technology , Mesra , Ranchi-835 215 , Jharkhand , India . Email: drvenkatesanj@gmail.com ; Tel: +91 9470137264.
Abstract:
A series of 2-methoxy-4-(5-phenyl-4,5-dihydro-1H-pyrazol-3-yl)phenol (pyrazoline) derivatives (2-6) have been synthesized and tested for human monoamine oxidase (hMAO) inhibitory activity. The most active derivative (2) behaved as a competitive hMAO-A inhibitor, with an inhibition constant value of 0.08 μM and a strong hMAO-A selectivity (Ki(hMAO-B)/Ki(hMAO-A) > 1751). In addition, 2 exhibited little to no cytotoxic effects up to a 25 μM concentration and provided the best blood-brain barrier permeability among the derivatives synthesized. Molecular dynamics simulations revealed that a chlorine substituent at the para-position of the phenyl ring in 2 enabled a π-π stacking interaction with Tyr407 and Tyr444 that resulted in the formation of an "aromatic sandwich" structure. Consequently, this tight-binding aromatic cage culminated in a dramatically reduced active site volume that is believed to be the origin of the observed selectivity between the hMAO-A and hMAO-B isozymes. Removal of the chlorine from 2 disrupted the favorable intermolecular interactions and resulted in a selectivity change towards hMAO-B.
Related Concept Videos
Eukaryotic Transcription Inhibitors
Eukaryotic transcription inhibitors usually contain two distinct domains, a...
What is Natural Selection?
Antibiotic Selection
Types of Selection
Frequency-dependent Selection
Dipeptidyl Peptidase 4 Inhibitors

