4-(2-(2-İzopropil-5-metilfenoksi) fenoksi) ftalonitril'in Alzheimer ve COVID-19 Enzimleriyle Moleküler Yerleştirme ve DFT Çalışmaları

Year 2025, Volume: 15 Issue: 3, 1008 - 1018, 01.09.2025

Aslıhan Aycan Tanrıverdi , Ümit Yıldıko

https://doi.org/10.21597/jist.1561684

Abstract

Ftalonitriller, yüksek performanslı makromoleküllerin sentez ve formülasyonunda önemli bir bileşendir. Moleküler yapılar üzerine sistematik teorik çalışma, yeni terapötik bileşiklerin rasyonel bir şekilde yaratılması için esastır. Bu çalışma, yoğunluk fonksiyonel teorisi (DFT) ve moleküler yerleştirme üzerine sistematik teorik araştırma yürütmek için aromatik nitril tipi 4-(2-(2-İzopropil-5-metilfenoksi)fenoksi)ftalonitril (IMPN) kullanır. IMPN'nin geometri açısından optimize edilmiş yapıları, 6-311G(d,p) baz setiyle DFT/B3LYP ve B3PW91 yöntemleri kullanılarak incelenmiştir. MEP sonuçları, metilfenoksinin elektronik etkisinin siyano gruplarından elektronları çektiğini ve bunun da siyano karbonunu daha fazla açığa çıkardığını ve nükleofilik reaksiyona daha yatkın hale getirdiğini göstermektedir. Temsili farmakolojik olarak aktif bir kısım olan IMPN'nin moleküler yerleştirme analizi ve farmakolojik potansiyeli, asetilkolinesteraz (AChE) ve bütirilkolinesteraz (BChE) Alzheimer ve COVID-19 enzimlerine karşı inhibe edici kapasitesini belirlemek için değerlendirildi. Bir ligand olarak IMPN, enzim kristal yapılarıyla -8.243, -7.920 ve -7.368 kcal/mol'lük etkili yerleştirme puanları gösterdi.

Keywords

Ftalonitril , DFT hesaplamaları , Moleküler yerleştirme

Molecular docking of 4-(2-(2-Isopropyl-5-methylphenoxy) phenoxy) phthalonitrile with Alzheimer's and COVID-19 enzymes and DFT studies

Abstract

Phthalonitriles are a crucial component in the synthesis and formulation of high-performance macromolecules. Systematic theoretical study on molecular structures is essential for the rational creation of novel therapeutic compounds. This study takes aromatic nitrile type 4-(2-(2-Isopropyl-5-methylphenoxy)phenoxy)phthalonitrile (IMPN) to conduct systematic theoretical research on density functional theory (DFT) and molecular docking. The geometry-optimized structures of IMPN were examined using the DFT/B3LYP and B3PW91 methods with the 6-311G(d,p) basis set. The MEP results show that the electronic effect of methylphenoxy attracts electrons from cyano groups, which makes the cyano carbon more exposed and more prone to nucleophilic reaction. The molecular docking analysis and pharmacological potential of IMPN, as a representative pharmacologically active moiety, were assessed to ascertain its inhibitory capacity against acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) Alzheimer's and COVID-19 enzymes. IMPN, as a ligand, demonstrated effective docking scores of -8.243, -7.920, and -7.368 kcal/mol with the enzyme crystal structures.

Keywords

Phthalonytrile , DFT calculations , Molecular docking

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