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

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.

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

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.

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