Synthesis and Characterization of New Pyrrole Derivatives, and Investigation of Their Monoamine Oxidase Inhibition Properties and Molecular Docking Studies

Year 2022, , 180 - 187, 01.06.2022

Derya Osmaniye , Yusuf Özkay

https://doi.org/10.26453/otjhs.986753

Abstract

Objective: Depression is an important psychiatric disease and its incidence is high in the world. According to the World Health Organization, 350 million people are diagnosed with depression. The use of monoamine oxidase inhibitors in this field also makes the development of new compounds valuable.
Materials and Methods: Pyrrole derivative (2a-2e) compounds consisting of 5 new molecules were synthesized. The structures of the obtained compounds were elucidated using spectroscopic methods. The in vitro monoamine oxidase enzyme inhibitory activities of the compounds were investigated.
Results: Among the synthesized compounds, compounds 2b and 2c showed significant inhibitory activity against monoamine oxidase-A enzyme.
Conclusion: When the selective monoamine oxidase-A inhibitor potentials of the synthesized compounds are examined; it is seen that promising results have been achieved. It is planned to reach more effective new compounds with the modifications made on the obtained compounds.  

Keywords

Depression, docking, monoamine oxidase, monoamine oxidase inhibitors

Yeni Pirol Türevlerinin Sentezi ve Karakterizasyonu, Monoamin Oksidaz İnhibisyon Özelliklerinin ve Moleküler Doking Çalışmalarının Araştırılması

Abstract

Amaç: Depresyon önemli bir psikiyatrik hastalıktır ve dünyada görülme sıklığı yüksektir. Dünya Sağlık Örgütü tarafından, 2012 yılında yaklaşık 350 milyon kişinin depresyon ile mücadele ettiğini belirtilmiştir. Özellikle monoamin oksidaz-A inhibitörleri depresyon tedavisinde kullanılmaktadır. Monoamin oksidaz inhibitörlerinin bu alanda kullanımı, yeni bileşiklerin geliştirilmesini de değerli kılmaktadır.
Materyal ve Metot: 5 yeni molekülden oluşan pirol türevi (2a-2e) bileşikler sentezlenmiştir. Elde edilen bileşiklerin yapıları spektroskopik yöntemler kullanılarak aydınlatılmıştır. Bileşiklerin in vitro monoamin oksidaz enzim inhibitor etkinlikleri incelenmiştir.
Bulgular: Sentezlenen bileşikler içerisinde 2b ve 2c kodlu bileşikler monoamin oksidaz-A enzimine karşı önemli düzeyde inhibitor etkinlik göstermiştir.
Sonuç: Sentezlenen bileşiklerin selektif monoamin oksidaz-A inhibitör potansiyelleri incelendiğinde umut verici sonuçlara ulaşıldığı görülmektedir. Elde edilen bileşikler üzerinde yapılan modifikasyonlar ile daha etkili yeni bileşiklere ulaşılması planlanmaktadır. 

Keywords

Depresyon, doking, monoaminoksidaz, monoamin oksidaz inhibitörleri

References

• Hampel H, Berger C, Buch K, Möller HJ. A review of the reversible MAO A inhibitor moclobemide in geriatric patients. Human Psychopharmacology Clin Exp. 1998;13(1):43-51. doi:10.1002/(SICI)1099-1077(199801)13:1<43::AID-HUP953>3.0.CO;2-Z
• El-Halaby LO, El-Husseiny WM, El-Messery SM, Goda FE. Biphenylpiperazine based MAO inhibitors: synthesis, biological evaluation, reversibility and molecular modeling studies. Bioorg Chem. 2021;105216. doi:10.1016/j.bioorg.2021.105216
• Shulman KI, Herrmann N, Walker SE. Current place of monoamine oxidase inhibitors in the treatment of depression. CNS Drugs. 2013;27(10):789-797. doi:10.1007/s40263-013-0097-3
• Bonnet U. Moclobemide: therapeutic use and clinical studies. CNS Drug Rev. 2003;9(1):97-140. doi:10.1111/j.1527-3458.2003.tb00245.x
• Li W, Guo B, Tao K, ve ark. Inhibition of SIRT1 in hippocampal CA1 ameliorates PTSD-like behaviors in mice by protections of neuronal plasticity and serotonin homeostasis via NHLH2/MAO-A pathway. Biochem Biophys Res Commun. 2019;518(2):344-350. doi:10.1016/j.bbrc.2019.08.060
• Yamali C, Engin FS, Bilginer S, ve ark. Phenothiazine-based chalcones as potential dual-target inhibitors toward cholinesterases (AChE, BuChE) and monoamine oxidases (MAO-A, MAO-B). J Heterocycl Chem. 2021;58(1):161-171. doi:10.1002/jhet.4156
• Takao K, Sakatsume T, Kamauchi H, Sugita Y. Syntheses and evaluation of 2-or 3-(N-cyclicamino) chromone derivatives as monoamine oxidase inhibitors. Chem Pharm Bull. 2020;68(11):1082-1089. doi:10.1248/cpb.c20-00579
• Salgin-Goksen U, Telli G, Erikci A, ve ark. New 2-pyrazoline and hydrazone derivatives as potent and selective monoamine oxidase A inhibitors. J Med Chem. 2021;64(4):1989-2009. doi:10.1021/acs.jmedchem.0c01504
• Aggarwal NN, Dkhar Gatphoh BF, Kumar MV, Ghetia S, Revanasiddappa B. Synthesis, in silico analysis and antidepressant activity of pyrazoline analogs. Thai J Pharm Sci. 2021;45(1). doi:10.3329/dujps.v19i2.50634
• Delogu GL, Kumar A, Gatto G, ve ark. Synthesis and in vitro study of nitro-and methoxy-2-phenylbenzofurans as human monoamine oxidase inhibitors. Bioorg Chem. 2021;107:104616. doi:10.1016/j.bioorg.2020.104616
• Sağlık BN, Çavuşoğlu BK, Osmaniye D, ve ark. In vitro and in silico evaluation of new thiazole compounds as monoamine oxidase inhibitors. Bioorg Chem. 2019;85:97-108. doi:10.3390/molecules25184342
• Can ÖD, Osmaniye D, Özkay ÜD, ve ark. MAO enzymes inhibitory activity of new benzimidazole derivatives including hydrazone and propargyl side chains. Eur J Med Chem. 2017;131:92-106. doi:10.1016/j.ejmech.2017.03.009
• Can NÖ, Osmaniye D, Levent S, ve ark. Design, synthesis and biological assessment of new thiazolylhydrazine derivatives as selective and reversible hMAO-A inhibitors. Eur J Med Chem. 2018;144:68-81. doi:10.1016/j.ejmech.2017.12.013
• Ilgın S, Osmaniye D, Levent S, ve ark. Design and synthesis of new benzothiazole compounds as selective hMAO-B inhibitors. Molecules. 2017;22(12):2187. doi:10.3390/molecules22122187
• Can NÖ, Osmaniye D, Levent S, ve ark. Synthesis of new hydrazone derivatives for MAO enzymes inhibitory activity. Molecules. 2017;22(8):1381. doi:10.3390/molecules22081381
• Tok F, Uğraş Z, Sağlık BN, Özkay Y, Kaplancıklı ZA, Koçyiğit-Kaymakçıoğlu B. Novel 2, 5-disubstituted-1, 3, 4-oxadiazole derivatives as MAO-B inhibitors: synthesis, biological evaluation and molecular modeling studies. Bioorg Chem. 2021;112:104917. doi:10.1016/j.bioorg.2021.104917
• Tok F, Sağlık BN, Özkay Y, Ilgın S, Kaplancıklı ZA, Koçyiğit-Kaymakçıoğlu B. Synthesis of new hydrazone derivatives and evaluation of their monoamine oxidase inhibitory activity. Bioorg Chem. 2021:105038. doi:10.1016/j.bioorg.2021.105038
• Son S-Y, Ma J, Kondou Y, Yoshimura M, Yamashita E, Tsukihara T. Structure of human monoamine oxidase A at 2.2-Å resolution: the control of opening the entry for substrates/inhibitors. PNAS. 2008;105(15):5739-44. doi:10.1073/pnas.0710626105
• Schrödinger Release 2020-1: Glide; Schrödinger, LLC: New York, NY, USA; 2020.
• Schrödinger Release 2020-1: QikProp; Schrödinger, LLC: New York, NY, USA; 2020.
• Çavuşoğlu BK, Sağlık BN, Osmaniye D, ve ark. Synthesis and biological evaluation of new thiosemicarbazone derivative schiff bases as monoamine oxidase inhibitory agents. Molecules. 2018;23(1):60. doi:10.3390/molecules23010060
• Mathew B, Baek SC, Lee JP, ve ark. Selected aryl thiosemicarbazones as a new class of multi-targeted monoamine oxidase inhibitors. Med Chem Comm. 2018;9(11):1871-81. doi:10.1039/c8md00399h
• Altintop MD, Sever B, Osmaniye D, Sağlık BN, Özdemir A. Design, synthesis, in vitro and in silico evaluation of new pyrrole derivatives as monoamine oxidase inhibitors. Arch Pharm. 2018;351(7):1800082. doi:10.1002/ardp.201800082
• Qazi SU, Naz A, Hameed A, ve ark. Semicarbazones, thiosemicarbazone, thiazole and oxazole analogues as monoamine oxidase inhibitors: Synthesis, characterization, biological evaluation, molecular docking, and kinetic studies. Bioorg Chem. 2021;115:105209. doi:10.1016/j.bioorg.2021.105209
• Osmaniye D, Kurban B, Sağlık BN, ve ark. Novel thiosemicarbazone derivatives: In vitro and ın silico evaluation as potential MAO-B inhibitors. Molecules. 2021;26(21):6640. doi:10.3390/molecules26216640