PTDP'nin Alzheimer Hastalığı Tedavisindeki Önemi: Kuantum Hesaplamaları, ADME Profili ve Moleküler Yerleştirme Yaklaşımları

Öz

Alzheimer hastalığı (AH), öğrenmeyi, hafızayı ve davranışı önemli ölçüde etkileyen yaşa bağlı nörodejeneratif bir beyin bozukluğudur. Bu çalışmada molekül, **N-fenil-5-(1H-pirol-2-il)-3-(p-tolil)-4,5-dihidro-1H-pirazol-1-karbotioamid (PTDP) **, AD için potansiyel bir inhibitör olarak değerlendirildi. Yoğunluk fonksiyonel teorisi (DFT) hesaplamaları, 6-311G(d,p) temel seti ile B3LYP ve B3PW91 fonksiyonel yöntemleri kullanılarak yapıldı. Termal özellikler, HOMO-LUMO enerji seviyeleri, dipol momenti, polarize edilebilirlik, kimyasal reaktivite tanımlayıcıları ve moleküler elektrostatik potansiyel (MEPS) gibi temel parametreler hesaplandı ve görselleştirildi. PTDP molekülü için enerji açığı (∆E), B3LYP yöntemiyle 3,603 eV ve B3PW91 yöntemiyle 3,977 eV olarak belirlendi ve bu, onun elektronik özellikleri ve reaktivitesi hakkında önemli bilgiler sağladı. Ek olarak, doğrusal olmayan optik (NLO) özellikler, işlevsel yönteme bağlı farklılıklar sergilerken, B3LYP hesaplaması yüksek bir x bileşeni dipol momenti (5,9430 D) gösterirken, B3PW91 yöntemi elektron yoğunluğu dağılımında daha fazla asimetri ortaya çıkardı. Bu bulgular PTDP'nin AD tedavisi ve NLO uygulamaları için potansiyelini göstermektedir. Moleküler yerleştirme sonuçları ayrıca PTDP'nin reseptör molekülüne karşı iyi bir bağlanma profiline sahip olduğunu gösterdi. İlaç keşfi ve geliştirilmesinde önemli olan ADMET analizi kullanılarak PTDP molekülünün farmakokinetik özellikleri de incelenmiştir. Ek olarak enerji çerçeveleri, moleküler yerleştirme sonuçları ve DFT hesaplaması yapıldı ve sonuçlar pirazol karbotiyoamid grubunun Alzheimer hastalığı (AD) aktivitesi için önemli olduğunu gösterdi.

Anahtar Kelimeler

• Alzheimer Hastalığı
• DFT
• Moleküler Modelleme
• Pirazol

Importance of PTDP in Alzheimer's Disease Treatment: Quantum Calculations, ADME Profile, and Molecular Docking Approaches

Öz

Alzheimer's disease (AD) is an age-related neurodegenerative brain disorder that significantly affects learning, memory, and behavior. In this study, molecule, **N-phenyl-5-(1H-pyrrol-2-yl)-3-(p-tolyl)-4,5-dihydro-1H-pyrazole-1-carbothioamide (PTDP)**, was evaluated as a potential inhibitor for AD. Density functional theory (DFT) calculations were performed using the B3LYP and B3PW91 functional methods with the 6-311G(d,p) basis set. Key parameters such as thermal properties, HOMO-LUMO energy levels, dipole moment, polarizability, chemical reactivity descriptors, and molecular electrostatic potential (MEPS) were computed and visualized. The energy gap (∆E) for the PTDP molecule was determined as 3.603 eV with the B3LYP method and 3.977 eV with the B3PW91 method, providing significant insights into its electronic properties and reactivity. Additionally, non-linear optical (NLO) properties demonstrated functional method-dependent variations, with the B3LYP calculation showing a high x-component dipole moment (5.9430 D), while the B3PW91 method revealed greater asymmetry in electron density distribution. These findings suggest PTDP's potential for AD treatment and NLO applications. Molecular docking results also showed that PTDP has a good binding profile towards the receptor molecule. Pharmacokinetic properties of the PTDP molecule were also examined using ADMET analysis, which is important in drug discovery and development. Additionally, energy frameworks, molecular docking results and DFT calculation were performed, and the results showed that the pyrazole carbothioamide group is important for Alzheimer's disease (AD) activity.

Anahtar Kelimeler

• Alzheimer Disease
• DFT
• Molecular Modelling
• Pyrazole

Kaynakça

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