Aim and objective: Depression is a momentous disease that can greatly reduce the quality
of life and cause death. In depression, neurotransmitter levels such as serotonine, dopamine and
noradrenaline are impaired. Monoamine oxidases (MAO) are responsible for oxidative catalysis of
these monoamine neurotransmitters. Because of this relation, MAO-A inhibitors show antidepressant
activity by regulating neurotransmitter levels. This study was carried out to investigate the design,
synthesis and activity of new antidepressant compounds in pyrazoline and hydrazone structure.
Material and method: Chalcones and hydrazides were heated under reflux to give new pyrazoline
and hydrazone derivatives. Docking simulations were performed using AutoDock4.2.
hMAO activities were determined by a fluorimetric method. To determine cell viability,
3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay was used. Behavioral
activities of the three compounds were determined by using Forced Swim Test, Step-Through
Passive Avoidance Test, Elevated Plus Maze and Open Field Arena Tests.
Results: According to in vitro tests, all of the synthesized compounds were found more potent than
moclobemide and six of the synthesized compounds were found more selective than moclobemide.
Three of the synthesized compounds were investigated for their behavioral activities comparing with
moclobemide after 7 days of i.p. treatment at 30 mg/kg. One of the three compounds elicited
significant antidepressant properties.
Conclusion: All of the synthesized compounds were found potent hMAO-A inhibitors in in vitro
screening tests. Only one of the in vivo tested three compounds, (3-(2-hydroxy-5-methylphenyl)-5-
p-tolyl-4,5-dihydropyrazol-1-yl)(pyridin-4-yl) methanone indicated significant antidepressant
activity. This article opens a window for further development of new pyrazoline and hydrazone
derivatives as antidepressant agents.