New Human Monoamine Oxidase A Inhibitors with Potential Anti- Depressant Activity: Design, Synthesis, Biological Screening and Evaluation of Pharmacological Activity

Title:New Human Monoamine Oxidase A Inhibitors with Potential Anti- Depressant Activity: Design, Synthesis, Biological Screening and Evaluation of Pharmacological Activity

Volume: 20 Issue: 6

Author(s): Begum Evranos-Aksoz *, Gulberk Ucar, Sadik Taskin Tas, Erkan Aksoz, Kemal Yelekci, Acelya Erikci, Yildirim Sara and Alper Bektas Iskit

Affiliation:

• Medicines and Medical Devices Agency, Analyses and Control Laboratories, Sıhhiye 06100, Ankara,Turkey

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

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.

Cite this article as:

Evranos-Aksoz Begum *, Ucar Gulberk, Tas Taskin Sadik , Aksoz Erkan , Yelekci Kemal , Erikci Acelya , Sara Yildirim and Iskit Bektas Alper, New Human Monoamine Oxidase A Inhibitors with Potential Anti- Depressant Activity: Design, Synthesis, Biological Screening and Evaluation of Pharmacological Activity, Combinatorial Chemistry & High Throughput Screening 2017; 20 (6) . https://dx.doi.org/10.2174/1386207320666170504113158