Quantum Chemical Calculation And Molecular Docking Studies Of Coumarin Based Curcumins As α-Glucosidase Inhibitors

Öz

This study aimed to investigate the physicochemical, structural, and electronic properties, and in silico assessment of molecular docking studies of six coumarin-based ethylcurcumin derivatives (C1-C6) as α-glucosidase inhibitors. The ground state geometries and chemical reactivity parameters of the compounds were calculated using the Lee–Yang–Parr, B3LYP hybrid functional with 6-311⁺⁺G(2d, 2p) basis set through Density Functional Theory (DFT) approach using the Gaussian 09 W. In addition, HOMO-LUMO energy levels and molecular electrostatic potential (MEP) analysis were performed to identify electrophilic and nucleophilic reactive sites. The ADMET (absorption, distribution, metabolism, elimination, and toxicity) profiles and pharmacokinetic parameters of all compounds were predicted through in silico calculations using the SwissADME and Pro Tox-3.0 web servers. Molecular docking analysis was performed for all compounds against the target protein (PDB ID: 3A4A) using AutoDock Vina (version 1.5.7). The docking results revealed that all compounds (C1-C6) exhibited strong interactions with the 3A4A receptor. Computational studies showed that compound C5 had the highest binding energy (-9.9 kcal/mol) in the molecular docking. Curcumin compounds, identified as having potential antidiabetic properties, exhibited higher binding energies against the 3A4A receptor than the reference compound acarbose, based on molecular docking analysis. The antidiabetic effects of curcumin-derived compounds are promising for future drug candidate molecules.

Anahtar Kelimeler

• Curcumin
• Density Functional Theory
• α-glucosidase
• Molecular Docking.

Kumarin Bazlı Kurkuminlerin α-Glukozidaz İnhibitörleri Olarak Kuantum Kimyasal Hesaplamaları ve Moleküler Yerleştirme Çalışmaları

Öz

Bu çalışmada altı kumarin bazlı etil kurkumin türevlerinin (C1-C6) fizikokimyasal, yapısal ve elektronik özelliklerinin araştırılması ve in silico moleküler yerleştirme çalışmalarıyla α-glukozidaz inhibitörü olarak değerlendirilmesi amaçlanmıştır. Bileşiklerin temel durum geometrileri ve kimyasal reaktivite parametreleri, Gaussian 09 W'da, Yoğunluk Fonksiyonel Teorisi (DFT) yaklaşımı kullanılarak, standart baz seti 6-311⁺⁺G(2d,2p) sahip B3LYP hibrit fonksiyoneli kullanılarak hesaplanmıştır. Buna ek olarak, elektrofilik ve nükleofilik reaktif bölgeleri belirlemek için HOMO-LUMO enerji seviyeleri ve moleküler elektrostatik potansiyel (MEP) analizi gerçekleştirilmiştir. ADMET (emilim, dağıtım, metabolizma, eliminasyon ve toksisite) profili ve farmakokinetik parametreler, SwissADME ve ProTox-3.0 web sunucusu kullanılarak tüm bileşikler için tahmin edilmiştir. AutoDock Vina 1.5.7 kullanılarak, tüm bileşikler için PDB ID: 3A4A'ya karşı moleküler yerleştirme analizi gerçekleştirilmiştir. Yapılan moleküler yerleştirme çalışmaları sonucunda, C1-C6 bileşikleri 3A4A reseptörü ile güçlü etkileşimler ortaya koymuştur. Hesaplamalı çalışmalar, C5 bileşiğinin moleküler yerleştirmede en yüksek bağlanma enerjisine (-9,9 kcal/mol) sahip olduğunu göstermiştir. Potansiyel antidiyabetik özelliklere sahip olduğu tespit edilen kurkumin bileşikleri, moleküler yerleştirme analizine göre 3A4A reseptörüne karşı referans bileşik akarboza göre daha yüksek bağlanma enerjisi göstermiştir. Kurkumin türevi bileşiklerin antidiyabetik etkileri, gelecekteki ilaç adayı moleküller için umut vericidir.

Anahtar Kelimeler

• Kurkumin
• Yoğunluk Fonksiyonel Teorisi
• α-glukozidaz
• Moleküler Yerleştirme

Kaynakça

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