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.
Combinatorial Chemistry & High Throughput Screening
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.
Export Options
About this article
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
DOI https://dx.doi.org/10.2174/1386207320666170504113158 |
Print ISSN 1386-2073 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5402 |
Call for Papers in Thematic Issues
Artificial Intelligence Methods for Biomedical, Biochemical and Bioinformatics Problems
Recently, a large number of technologies based on artificial intelligence have been developed and applied to solve a diverse range of problems in the areas of biomedical, biochemical and bioinformatics problems. By utilizing powerful computing resources and massive amounts of data, methods based on artificial intelligence can significantly improve the ...read more
Emerging trends in diseases mechanisms, noble drug targets and therapeutic strategies: focus on immunological and inflammatory disorders
Recently infectious and inflammatory diseases have been a key concern worldwide due to tremendous morbidity and mortality world Wide. Recent, nCOVID-9 pandemic is a good example for the emerging infectious disease outbreak. The world is facing many emerging and re-emerging diseases out breaks at present however, there is huge lack ...read more
Exploring Spectral Graph Theory in Combinatorial Chemistry
Scope of the Thematic Issue: Combinatorial chemistry involves the synthesis and analysis of a large number of diverse compounds simultaneously. Traditional methods rely on brute force experimentation, which can be time-consuming and resource-intensive. Spectral Graph Theory, a branch of mathematics dealing with the properties of graphs in relation to the ...read more
Integrating Network Pharmacology and Traditional Medicine: A New Perspective in Drug Mechanism Research
Network pharmacology is a network construction and network topology analysis strategy that combines pharmacology and pharmacodynamics. In recent years, network pharmacology has emerged as a powerful tool that can be integrated with pharmacology. Natural products commonly function in multicomponent, multitarget, and multipathway systems. Some examples encompass Ayurveda, traditional Chinese medicines ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Contemporary Management of Hypertension - How to Optimize Therapy
Cardiovascular & Hematological Disorders-Drug Targets Membrane Interactions of Oligomeric Alpha-Synuclein: Potential Role in Parkinsons Disease
Current Protein & Peptide Science Effects of Eugenol on the Central Nervous System: Its Possible Application to Treatment of Alzheimers Disease, Depression, and Parkinsons Disease
Current Bioactive Compounds High Content Screening for G Protein-Coupled Receptors Using Cell-Based Protein Translocation Assays
Combinatorial Chemistry & High Throughput Screening Diet-Induced Hyperhomocysteinemia Increases Amyloid-β Formation and Deposition in a Mouse Model of Alzheimers Disease
Current Alzheimer Research Antibiotic Properties and Applications of Lactoferrin
Current Pharmaceutical Design A Review: G-Quadruplex’s Applications in Biological Target Detection and Drug Delivery
Current Topics in Medicinal Chemistry Metals and Parkinson's Disease: Mechanisms and Biochemical Processes
Current Medicinal Chemistry INNO-206 (DOXO-EMCH), an Albumin-Binding Prodrug of Doxorubicin Under Development for Phase II Studies
Current Bioactive Compounds Adjudin - A Male Contraceptive with Other Biological Activities
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Discovery of GPCR Ligands by Molecular Docking Screening: Novel Opportunities Provided by Crystal Structures
Current Topics in Medicinal Chemistry Plant and Animal Steroids a New Hope to Search for Antiviral Agents
Current Medicinal Chemistry Editorial [Hot Topic: Food and Addiction: Implications and Relevance to Eating Disorders and Obesity (Guest Editor: Nicole M. Avena)]
Current Drug Abuse Reviews Highly Selective MEK Inhibitors
Current Enzyme Inhibition Overcoming Resistance to EGFR Inhibitors in NSCLC
Reviews on Recent Clinical Trials Zinc Hydrogen Sulfate Promoted Multi-component Preparation of Highly Functionalized Piperidines
Letters in Organic Chemistry The Role of T and B Cells in Atherosclerosis: Potential Clinical Implications
Current Pharmaceutical Design Physiologically Based Mathematical Models to Optimize Therapies Against Metastatic Colorectal Cancer: A Mini-Review
Current Pharmaceutical Design SYMPOSIA
Adolescent Psychiatry Editorial [Hot Topic: New Ligands at 5-HT and DA Receptors for the Treatment of Neuropsychiatric Disorders (Guest Editor: Giuseppe Di Giovanni) ]
Current Topics in Medicinal Chemistry