IN SILICO APPROACHES ON PHENYLALANINE HYDROXYLASE INHIBITOR-RELATED COMPOUNDS USED IN PARKINSON’S DISEASE TREATMENT

Öz

Objective: In Parkinson’s disease, Levodopa with Carbidopa addresses dopamine deficiency. Phenylalanine hydroxylase catalyzes phenylalanine to tyrosine conversion crucial for dopamine synthesis. Inhibiting phenylalanine hydroxylase may enhance Carbidopa's effects, preventing peripheral dopamine synthesis. The study used virtual scanning, molecular docking, and dynamics simulation to explore phenylalanine hydroxylase interactions with Carbidopa and similar ligands. ADME/T assessments and drug similarity tests were conducted to evaluate therapeutic potential in biological systems. Material and Method: A molecular docking study was performed on the structures obtained from the PubChem database and human PAH (PDB ID: 6PAH) using Autodock Vina within Chimera 1.16. Furthermore, the ligands underwent ADME/T assays, which are crucial aspects in drug development. Result and Discussion: The study suggests that 2-(2-Aminohydrazinyl)-3-(3,4-dihydroxyphenyl)-2-methylpropanoic acid shows promise as a phenylalanine hydroxylase inhibitor for Parkinson's disease treatment, but further research is needed to assess its safety, efficacy, and specificity, particularly in extracerebral regions, while also exploring its potential to improve the effectiveness of Levadopa/Carbidopa combination therapy.

Anahtar Kelimeler

• Drug development
• inhibitor
• in silico
• Parkinson
• phenylalanine hydroxylase

PARKİNSON HASTALIĞI TEDAVİSİNDE KULLANILAN FENİLALANİN HİDROKSİLAZ İNHİBİTÖRÜ İLE İLİŞKİLİ BİLEŞİKLERE İLİŞKİN İN SİLİKO YAKLAŞIMLAR

Öz

Amaç: Parkinson hastalığında, Levodopa ile Carbidopa kullanılarak dopamin eksikliği ele alınır. Fenilalanin hidroksilaz, dopamin sentezi için önemli olan fenilalanin'in tirozin'e dönüşümünü katalizler. Fenilalanin hidroksilaz'ın inhibe edilmesi, periferik dopamin sentezini engelleyerek Carbidopa'nın etkilerini artırabilir. Çalışmada, fenilalanin hidroksilazın Carbidopa ve benzeri ligandlarla etkileşimlerini araştırmak için sanal tarama, moleküler bağlanma ve dinamik simulasyon kullanıldı. ADME/T değerlendirmeleri ve ilaç benzerlik testleri biyolojik sistemlerdeki terapötik potansiyeli değerlendirmek amacıyla yapıldı. Gereç ve Yöntem: PubChem veritabanından elde edilen yapılar ve insan fenialanin hidroksilaz (PDB Kimlik Numarası: 6PAH) üzerinde bir moleküler bağlanma çalışması, Autodock Vina'nın Chimera 1.16 içinde kullanılarak gerçekleştirildi. Ayrıca, ligandlar ilaç geliştirme sürecinde önemli bir aşama olan ADME/T analizlerine tabi tutuldu. Sonuç ve Tartışma: Çalışma, 2-(2-Aminohydrazinyl)-3-(3,4-dihydroxyphenyl)-2-methylpropanoic acid'in Parkinson hastalığının tedavisinde fenilalanin hidroksilaz inhibitörü olarak umut vadettiğini öne sürüyor. Ancak, özellikle ekstraserebral bölgelerde güvenlik, etkinlik ve özgünlük değerlendirmek için daha fazla araştırmaya ihtiyaç olduğunu ve aynı zamanda Levadopa/Carbidopa kombinasyon tedavisinin etkinliğini artırma potansiyelini keşfetmenin önemli olduğunu belirtiyor.

Anahtar Kelimeler

• Fenilalanin hidroksilaz
• ilaç geliştirme
• inhibitör
• in siliko
• Parkinson hastalığı

Kaynakça

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