Submit Manuscript  

Article Details


New hMAO-A Inhibitors with Potential Antidepressant Activity: Design, Synthesis, Biological Screening and Evaluation of Pharmacological Activity

Author(s):

Begüm Evranos Aksöz , Gülberk Uçar, Sadık Taşkın Taş, Erkan Aksöz, Kemal Yelekçi, Açelya Erikçi, Yıldırım Sara and Alper Bektas İskit   Pages 1 - 13 ( 13 )

Abstract:


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.

Keywords:

MAO-A inhibitors, antidepressant activity, molecular docking, 2-pyrazoline, hydrazone

Affiliation:

Medicines and Medical Devices Agency - Analyses and Control Laboratories,06100, Sıhhıye Ankara, Department of Biochemistry, Faculty of Pharmacy, Hacettepe University, 06100, Sıhhıye Ankara, Department of Medical Pharmacology, Faculty of Medicine, Hacettepe University, 06100, Altindag Ankara, Medicines and Medical Devices Agency, Analyses and Control Laboratories, 06100, Sıhhıye Ankara, Faculty of Engineering and Natural Sciences, Department of Bioinformatics and Genetics (Head) Cibali Campus, Kadir Has University, 34083, Fatih İstanbul, Department of Biochemistry, Faculty of Pharmacy, Hacettepe University, 06100, Sıhhıye, Ankara, Department of Medical Pharmacology, Faculty of Medicine, Hacettepe University, 06100, Altindag Ankara, Department of Medical Pharmacology, Faculty of Medicine, Hacettepe University, 06100, Altindag Ankara



Read Full-Text article