[Home ] [Archive]   [ فارسی ]  
:: Main :: About :: Current Issue :: Archive :: Search :: Submit ::
Main Menu
Journal Information::
Articles Archive::
Guide for Authors::
For Reviewers::
Ethical Statements::
Site Facilities::
Contact us::
Search in website

Advanced Search
Receive site information
Enter your Email in the following box to receive the site news and information.
Copyright Policies




Open Access Policy

This journal provides immediate open access to its content on the principle that making research freely available to the public supports a greater global exchange of knowledge.

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License which allows users to read, copy, distribute and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited properly.

:: Volume 10, Issue 2 (Spring 2022) ::
Shefaye Khatam 2022, 10(2): 33-45 Back to browse issues page
Design of New Inhibitory Ligands of Monoamine Oxidase A-Enzyme for Use in the Control of Depression and Mental Disorders Using Bioinformatics Tools
Saeed Pirmoradi *
Department of Biochemistry, Shahid Chamran University of Ahvaz, Ahvaz, Iran , pirmoradi150@gmail.com
Abstract:   (1202 Views)
Introduction: Monoamine oxidase A-enzyme (MAO-A) and MAO-B inhibitors are involved in the treatment of some diseases of the nervous system and regulate the expression of cytokine genes associated with inflammation and various diseases. Materials and Methods: After selecting the inhibitory reference compound of MAO-A with the help of bioinformatic tools, such as ZINC15 and ZINCPHARMER, for virtual search through the structural and pharmacophoric properties of the reference inhibitory compound, several new ligands were obtained. Then, compariosn between the ligands with MAO-A docking process was performed and the selected top ligands in terms of toxicity, allergy, toxicity, and ADME prediction with tools, such as molsoft, PKCSM, way2drug swiss MADE, were examined. Results: Among the top four final ligands obtained, LIG52 had the highest interaction with different residues and with higher docking binding energy (vina score = -9.7) than the others, followed by IG48 and LIG54. Among the effective interacting residues, Trp128, ASN125, and GLU492 were bound to MAO-A in superior ligands, such as the reference compound. They also had the desired ability to interact with residues involved in substrate selectivity and catalytic activity, inhibition, and disruption of MAO-A activity. Conclusion: The ligands obtained in this study were able to have different interactions with the appropriate number of rotatable bonds on physicochemical properties and spatial orientation at the site of binding to MAO-A. Furthermore, the results obtained from different servers that investigated the molecular properties and drug similarity of toxicity and absorption of metabolism, secretion, and release of inhibitory ligand compounds were obtained. Therefore, they can be considered as possible drug compounds in biological systems after further studies in laboratory and clinical conditions.
Keywords: Ligands, Monoamine Oxidase, Nervous System, Drug Design
Full-Text [PDF 1567 kb]   (647 Downloads)    
Type of Study: Others --- Open Access, CC-BY-NC | Subject: Neuropharmacology
1. Tripathi, A. C., Upadhyay, S., Paliwal, S., and Saraf, S. K. Privileged Scaffolds as MAO Inhibitors: Retrospect and Prospects. Eur. J. Med. Chem. 2018; 145, 445-97. [DOI:10.1016/j.ejmech.2018.01.003]
2. Ramsay, R. R., and Albreht, A. Kinetics, Mechanism, and Inhibition of Monoamine Oxidase. J. Neural Transm. (Vienna) 2018; 125 (11), 1659-83. [DOI:10.1007/s00702-018-1861-9]
3. Binda C. L. M., Hubálek F., Restelli N., Edmondson D. E., and Mattevi A., "Insights into the mode of inhibition of human mitochondrial monoamine oxidase B from high-resolution crystal structures", Proc. Natl.Acad. Sci. .2003; 100 (17), 9750-5. [DOI:10.1073/pnas.1633804100]
4. Bortolato, M., Chen, K., and Shih, J. C. Monoamine Oxidase Inactivation: from Pathophysiology to Therapeutics. Adv. Drug Deliv. Rev. 2008; 60(13-14) 1527-33. [DOI:10.1016/j.addr.2008.06.002]
5. Dreiseitel A, Korte G, Schreier P, Oehme A, Locher S, Domani M, Hajak G. and Sand P.G, Berry anthocyanins and their aglycons inhibit monoamine oxidases A and B", Pharmacol. Res. 2009 59(5), 306-11. [DOI:10.1016/j.phrs.2009.01.014]
6. Bortolato, M., and Shih, J. C. Behavioral Outcomes of Monoamine Oxidase Deficiency: Preclinical and Clinical Evidence. Int. Rev. Neurobiol. 2011; 100, 13-42. [DOI:10.1016/B978-0-12-386467-3.00002-9]
7. Tipton, K. F. 90 Years of Monoamine Oxidase: Some Progress and Some Confusion. J. Neural Transm. (Vienna). 2018; 125 (11), 1519-51. [DOI:10.1007/s00702-018-1881-5]
8. Edmondson, D. E., and Binda, C. Monoamine Oxidases. Subcell Biochem. 2018; 87, 117-39. [DOI:10.1007/978-981-10-7757-9_5]
9. Pletscher, A. The Discovery of Antidepressants: a Winding Path.Experientia. 1991.47 (1), 4-8. [DOI:10.1007/BF02041242]
10. Vakili N, Asgari K, Kalantari M, Molavi H, Asheghan M. The Effect of Alexithymia, Anxiety, and Depression on Pain Severity in Female Patients with Fibromyalgia in Tehran. The Neuroscience Journal of Shefaye Khatam. 2015 Dec 10; 3(4): 49-56. [DOI:10.18869/acadpub.shefa.3.4.49]
11. Al-Nuaimi, S. K., Mackenzie, E. M., and Baker, G. B. Monoamine Oxidase Inhibitors and Neuroprotection: a Review. Am. J. Ther. 2012; 19 (6), 436-48. [DOI:10.1097/MJT.0b013e31825b9eb5]
12. Hasan, F., McCrodden, J. M., Kennedy, N. P., and Tipton, K. F. The Involvement of Intestinal Monoamine Oxidase in the Transport and Metabolism of Tyramine. J. Neural Transm. Suppl. 1988 26, 1-9.
13. Gillman, P. K. A Reassessment of the Safety Profile of Monoamine Oxidase Inhibitors: Elucidating Tired Old Tyramine Myths. J. Neural Transm. (Vienna). 2018. 125 (11), 1707-17. [DOI:10.1007/s00702-018-1932-y]
14. Anderson, M. C., Hasan, F., McCrodden, J. M., and Tipton, K. F. Monoamine Oxidase Inhibitors and the Cheese Effect. Neurochem. Res. 1993. 18(11), 1145-49. [DOI:10.1007/BF00978365]
15. Jalilvand M, Souri R, Solimanitabar M. The Effectiveness of Yoga Exercises on Anxiety and Depression in Patients with Psoriasis. The Neuroscience Journal of Shefaye Khatam. 2021 Mar 10;9(2):60-7. [DOI:10.52547/shefa.9.2.60]
16. Thomas Broome, S., Louangaphay, K., Keay, K. A., Leggio, G. M., Musumeci, G.,and Castorina, A. Dopamine: an Immune Transmitter. Neural Regen.Res. 2020. 15 (12), 2173-85. [DOI:10.4103/1673-5374.284976]
17. Lin, A., Song, C., Kenis, G., Bosmans, E., De Jongh, R., Scharpe, S., et al. The In Vitro Immunosuppressive Effects of Moclobemide in Healthy Volunteers.J. Affect Disord. 2000. 58 (1), 69-74. [DOI:10.1016/S0165-0327(99)00076-2]
18. Opal, S. M., and DePalo, V. A. Anti-inflammatory Cytokines. Chest. 2000. 117(4), 1162-72. [DOI:10.1378/chest.117.4.1162]
19. Trudler, D., Weinreb, O., Mandel, S. A., Youdim, M. B., and Frenkel, D. DJ-1 Deficiency Triggers Microglia Sensitivity to Dopamine toward a Proinflammatory Phenotype that Is Attenuated by Rasagiline. J. Neurochem. 2014. 129 (3), 434-47. [DOI:10.1111/jnc.12633]
20. Bielecka, A. M., Paul-Samojedny, M., and Obuchowicz, E. Moclobemide Exerts Anti-inflammatory Effect in Lipopolysaccharide-Activated Primary Mixed Glial Cell Culture. Naunyn Schmiedebergs Arch. Pharmacol. 2010. 382 (5-6), 409-17. [DOI:10.1007/s00210-010-0535-4]
21. Amirpour B, Aghayousefi A, Goli R, Abdolmaleki L. Biomarkers of Cardiovascular Responses among War Veterans with Posttraumatic Stress Disorder. The Neuroscience Journal of Shefaye Khatam. 2015 Dec 10;3(4): 57-64. [DOI:10.18869/acadpub.shefa.3.4.57]
22. Peehl, D. M., Coram, M., Khine, H., Reese, S., Nolley, R., and Zhao, H. The Significance of Monoamine Oxidase-A Expression in High-Grade Prostate Cancer. J. Urol. 2008. 180 (5), 2206-11. [DOI:10.1016/j.juro.2008.07.019]
23. Shih, J. C. Monoamine Oxidase Isoenzymes: Genes, Functions, and Targets for Behavior and Cancer Therapy. J. Neural Transm. (Vienna). 2018. 125 (11),1553-66. [DOI:10.1007/s00702-018-1927-8]
24. Wu, J. B., Yin, L., Shi, C., Li, Q., Duan, P., Huang, J. M., etal. MAA-dependent Activation of Shh-IL6-RANKL Signaling Network PromotesProstate Cancer Metastasis by Engaging Tumor-Stromal Cell Interactions.Cancer Cell 2017. 31 (3), 368-82. [DOI:10.1016/j.ccell.2017.02.003]
25. Carradori, S., and Petzer, J. P. Novel Monoamine Oxidase Inhibitors: a Patent Review (2012- 2014). Expert Opin. Ther. Pat. 2015. 25 (1), 91-110. [DOI:10.1517/13543776.2014.982535]
26. Carradori, S., Secci, D., and Petzer, J. P. MAO Inhibitors and Their Wider Applications: a Patent Review. Expert Opin. Ther. Pat. 2018. 28 (3), 211-26. [DOI:10.1080/13543776.2018.1427735]
27. Gealageas, R., Devineau, A., So, P. P. L., Kim, C. M. J., Surendradoss, J.,Buchwalder, C., et al. Development of Novel Monoamine Oxidase-B (MAO-B) Inhibitors with Reduced Blood-Brain Barrier Permeability for the Potential Management of Noncentral Nervous System (CNS) Diseases. J. Med. Chem. 2018. 61 (16), 7043-64. [DOI:10.1021/acs.jmedchem.7b01588]
28. Menazza, S., Blaauw, B., Tiepolo, T., Toniolo, L., Braghetta, P., Spolaore, B., et al. Oxidative Stress by Monoamine Oxidases Is Causally Involved in Myofiber Damage in Muscular Dystrophy. Hum. Mol. Genet. 2010. 19 (21),4207-4215. [DOI:10.1093/hmg/ddq339]
29. Deshwal, S., Di Sante, M., Di Lisa, F., and Kaludercic, N. Emerging Role of Monoamine Oxidase as a Therapeutic Target for Cardiovascular Disease. Curr.Opin. Pharmacol. 2017. 33, 64-9. [DOI:10.1016/j.coph.2017.04.003]
30. Detsi, A., Kontogiorgis, C., and Hadjipavlou-Litina, D. Coumarin Derivatives: an Updated Patent Review (2015-2016). Expert Opin. Ther. Pat.27.2017. (11), 1201-26. [DOI:10.1080/13543776.2017.1360284]
31. Yin, L., Li, J., Liao, C. P., and Jason Wu, B. Monoamine Oxidase Deficiency Causes Prostate Atrophy and Reduces Prostate Progenitor Cell Activity. Stem Cells. 2018. 36 (8), 1249-58. [DOI:10.1002/stem.2831]
32. Gábor Erdős, Zsuzsanna Dosztányi. Analyzing Protein Disorder with IUPred2A Current Protocols in Bioinformatics 2020; 70(1):e99. [DOI:10.1002/cpbi.99]
33. Refsgaard HHF, Jensen BF, Brockhoff PB, Padkjaer SB, Guldbrandt M, Chistensen MS. In silico prediction of membrane permeability from calculated molecular parameters. J Med Chem. 2005; 48(3): 805-11. [DOI:10.1021/jm049661n]
34. Debnath, Pharmacophore mapping of a series of 2,4-diamino-5-deazapteridine Inhibitors of mycobacterium avium complex dihydrofolate reductase, J. Med. Chem. 2002. 45 (1) 41-53. [DOI:10.1021/jm010360c]
35. Mousazadeh O, Haji Alizadeh K. Prediction of Depression Based on Dysfunctional Attitudes, Personality Traits, and Family Communication Patterns among Patients with Epilepsy. The Neuroscience Journal of Shefaye Khatam. 2017 Oct 10; 5(4): 47-56. [DOI:10.18869/acadpub.shefa.5.4.47]
36. Graff, L. A., Walker, J. R., and Bernstein, C. N. Depression and Anxiety in Inflammatory Bowel Disease: a Review of Comorbidity and Management.Inflamm. Bowel Dis. 2009. 15 (7), 1105-18. [DOI:10.1002/ibd.20873]
37. Kast, R. E. Crohn's Disease Remission with Phenelzine Treatment.Gastroenterology. 1998. 115 (4), 1034-5. [DOI:10.1016/S0016-5085(98)70292-6]
38. Dveksler GS, Pensiero MN, Cardellichio CB, Williams RK, Jiang GS, et al. Cloning of the mouse hepatitis virus (MHV) receptor: expression in human and hamster cell lines confers susceptibility to MHV. J Virol. 1991; 65:6881-91. [DOI:10.1128/jvi.65.12.6881-6891.1991]
39. Veber DF, Johnson SR, Cheng HY, Smith BR, Ward KW, Kapple KD. Molecular properties that influence the oral bioavailability of drug candidates. J Med Chem.2002; 45(12): 2615-23. [DOI:10.1021/jm020017n]
40. Hendrayani SF, Al-Harbi B, Al-Ansari MM, Silva G, Aboussekhra A. The inflammatory/cancer-related IL-6/STAT3/NF-κB positive feedback loop includes AUF1 and maintains the active state of breast myofibroblasts. Oncotarget. 2016; 7:41974-85. [DOI:10.18632/oncotarget.9633]
41. Zhang W, Zhao Y, Zhang F, Wang Q, Li T, Liu Z, Wang J, Qin Y, Zhang X, Yan X, et al. The use of anti-inflammatory drugs in the treatment of people with severe coronavirus disease 2019 (COVID-19): The perspectives of clinical immunologists from China. Clin. Immunol. 2020, 214, 108393. [CrossRef] [DOI:10.1016/j.clim.2020.108393]
42. Lai C.-C, Shih T.-P, Ko W.-C, Tang H.-J, Hsueh P.-R. Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) and coronavirus disease-2019 (COVID-19): The epidemic and the challenges. Int. J. Antimicrob.Agents 2020, 55, 105924. [CrossRef] [PubMed]. [DOI:10.1016/j.ijantimicag.2020.105924]
43. Daina A, Zoete V. A BOILED-Egg To Predict Gastrointestinal Absorption and Brain Penetration of Small Molecules. ChemMedChem. 2016. 11, 1117-21. [DOI:10.1002/cmdc.201600182]
44. Ritchie T. J, Ertl P, Lewis R. The graphical representation of ADME-related molecule properties for medicinal chemists. Drug Discov. Today . 2011.16, 65-72. [DOI:10.1016/j.drudis.2010.11.002]
45. Khosravi Z, Rahmatinejad P, Farah Bijari A. Comparing Quality of Intimate Relationship and Anger Experience in Patients with Borderline Personality and Bipolar-II Disorders. The Neuroscience Journal of Shefaye Khatam. 2015 Dec 10; 3(4): 1-9. [DOI:10.18869/acadpub.shefa.3.4.1]

XML   Persian Abstract   Print

Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:

pirmoradi S. Design of New Inhibitory Ligands of Monoamine Oxidase A-Enzyme for Use in the Control of Depression and Mental Disorders Using Bioinformatics Tools. Shefaye Khatam 2022; 10 (2) :33-45
URL: http://shefayekhatam.ir/article-1-2298-en.html

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Volume 10, Issue 2 (Spring 2022) Back to browse issues page
مجله علوم اعصاب شفای خاتم The Neuroscience Journal of Shefaye Khatam
Persian site map - English site map - Created in 0.05 seconds with 45 queries by YEKTAWEB 4642