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Journals / Afyon Kocatepe Üniversitesi Fen ve Mühendislik Bilimleri Dergisi / 2022 / Cilt: 22 - Sayı: 2

Synthesis, Characterization and Docking Studies of New Chalcone Derivatives Carrying Propargyl Side Chain as a Monoaminoxidase Inhibitor

Monoaminoksidaz İnhibitörü Olarak Propargil Yan Zinciri Taşıyan Yeni Şalkon Türevlerinin Sentezi, Karakterizasyonu ve Moleküler Modelleme Çalışmaları

Derya OSMANİYE
Begüm Nurpelin SAĞLIK
Pages
268–274
Publication Date
2022-10-12
DOI
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AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

With the molecular modelling studies carried out, the binding and interaction points of the compound 2c in the hMAO-B enzyme active site were determined.

📌 3 Key Takeaways

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Objective & Hypothesis:Monoamine oxidases (MAO) are a family of enzymes responsible for the oxidative deamination of endogenous and exogenous amines.
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Key Findings & Data:For this purpose, within the scope of this study, new propargyl-chalcone derivatives were synthesized and the structure determinations were elucidated using 1H-NMR, 13C-NMR and high-resolution mass spectroscopy (HRMS) methods.
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Conclusion & Impact:With the molecular modelling studies carried out, the binding and interaction points of the compound 2c in the hMAO-B enzyme active site were determined.
🔬Design:Modeling & Simulation
📍Scope:Comprehensive Sample
⚙️Variables:Domain Parameters

Abstract

Monoamine oxidases (MAO) are a family of enzymes responsible for the oxidative deamination of endogenous and exogenous amines. The MAO enzyme, which consists of two isoforms named MAO-A and MAO-B, are important targets in the development of drugs for the treatment of neuropsychiatric and neurodegenerative disorders due to their role in the metabolism of neurotransmitters. It is known that MAO-B inhibitors are frequently preferred in the treatment of the most common neurodegenerative diseases such as Parkinson's disease (PD) and Alzheimer's disease (AD). For this purpose, within the scope of this study, new propargyl-chalcone derivatives were synthesized and the structure determinations were elucidated using 1H-NMR, 13C-NMR and high-resolution mass spectroscopy (HRMS) methods. The data obtained as a result of in vitro activity tests showed that the compound 2c is promising as a selective MAO-B inhibitor. With the molecular modelling studies carried out, the binding and interaction points of the compound 2c in the hMAO-B enzyme active site were determined.

Özet

Monoamin oksidazlar (MAO), endojen ve ekzojen aminlerin oksidatif deaminasyonundan sorumlu enzim ailesidir. MAO-A ve MAO-B olarak isimlendirilen iki izoformdan oluşan MAO enzimi nörotransmiterlerin metabolizmasındaki rollerinden dolayı nöropsikiyatrik ve nörodejeneratif bozuklukların tedavisi için ilaçların geliştirilmesinde önemli hedeflerdir. Özellikle MAO-B inhibitörlerinin Parkinson hastalığı (PH) ve Alzheimer hastalığı (AH) gibi en sık görülen nörodejeneratif hastalıkların tedavisinde sıklıkla tercih edildiği bilinmektedir. Bu amaçla, bu çalışma kapsamında yeni propargil-şalkon türevleri sentezlenmiş ve yapı tayinleri 1H-NMR, 13C-NMR ve yüksek çözünürlüklü kütle spektroskopisi (HRMS) metotları kullanılarak aydınlatılmıştır. İn vitro aktivite testleri sonucunda elde edilen veriler 2c kodlu bileşiğin MAO-B inhibitörü olarak umut vaat edici olduğunu ortaya koymuştur. Gerçekleştirilen moleküler modelleme çalışmaları ile bileşik 2c’nin hMAO-B enzim aktif bölgesindeki bağlanma ve etkileşim noktaları belirlenmiştir.

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Cite This Article

OSMANİYE, D., SAĞLIK, B. N. (2022). Synthesis, Characterization and Docking Studies of New Chalcone Derivatives Carrying Propargyl Side Chain as a Monoaminoxidase Inhibitor. Afyon Kocatepe Üniversitesi Fen ve Mühendislik Bilimleri Dergisi, Cilt: 22 - Sayı: 2, 268–274. https://ajindex.com/articles/429591

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References (8)

  1. Binda, C., Wang, J., Pisani, L., Caccia, C., Carotti, A., Salvati, P.,. and Mattevi, A. 2007. Structures of human monoamine oxidase B complexes with selective noncovalent inhibitors: safinamide and coumarin analogs. Journal of medicinal chemistry, 50(23), 5848-5852.
  2. Can, Ö. D., Osmaniye, D., Özkay, Ü. D., Sağlık, B. N., Levent, S., Ilgın, S., Baysal, M., Özkay, Y. and Kaplancıklı, Z. A. 2017. MAO enzymes inhibitory activity of new benzimidazole derivatives including hydrazone and propargyl side chains. European journal of medicinal chemistry, 131, 92-106.
  3. Can, N. Ö., Osmaniye, D., Levent, S., Sağlık, B. N., Korkut, B., Atlı, Ö., Özkay, Y. and Kaplancıklı, Z. A. 2018. Design, synthesis and biological assessment of new thiazolyl hydrazine derivatives as selective and reversible hMAO-A inhibitors. European journal of medicinal chemistry, 144, 68-81.
  4. Çeçen, M., Oh, J. M., Özdemir, Z., Büyüktuncel, S. E., Uysal, M., Abdelgawad, M. A.,. and Kim, H. 2020.
  5. Design, Synthesis, and Biological Evaluation of Pyridazinones Containing the (2-Fluorophenyl) Piperazine Moiety as Selective MAO-B Inhibitors. Molecules, 25(22), 5371. Distinto, S., Meleddu, R., Yanez, M., Cirilli, R., Bianco, G., Sanna, M. L.,. and Maccioni, E. 2016. Drug design, synthesis, in vitro and in silico evaluation of selective monoaminoxidase B inhibitors based on 3-acetyl-2-dichlorophenyl-5-aryl-2, 3-dihydro-1, 3, 4-oxadiazole chemical scaffold. European journal of medicinal chemistry, 108, 542-552.
  6. Glide, Version 7.1, Schrödinger, LLC: New York, NY, USA, 2016.
  7. Guglielmi, P., Mathew, B., Secci, D. and Carradori, S. 2020. Chalcones: Unearthing their therapeutic possibility as monoamine oxidase B inhibitors. European Journal of Medicinal Chemistry, 112650. Hammuda, A., Shalaby, R., Rovida, S., Edmondson, D. E., Binda, C. and Khalil, A. 2016. Design and synthesis of novel chalcones as potent selective monoamine oxidase-B inhibitors. European journal of medicinal chemistry, 114, 162-169.
  8. Ilgın, S., Osmaniye, D., Levent, S., Sağlık, B. N., Acar Çevik, U., Çavuşoğlu, B. K., Özkay, Y. and Kaplancıklı, Z. A. 2017. Design and synthesis of new benzothiazole compounds as selective hMAO-B inhibitors. Molecules, 22(12), 2187. Jismy, B., El Qami, A., Pišlar, A., Kos, J., Gobec, S., Knez, D. and Abarbri, M. 2021. Pyrimido [1, 2-b] indazole derivatives: Selective inhibitors of human monoamine oxidase B with neuroprotective activity. European Journal of Medicinal Chemistry, 209, 112911. Kumar, B., Kumar, V.,