DPPH Antioxidant Assays, Molecular Docking Studies and ADMET Predictions of Some 4-Chloromethyl Substituted Coumarin Compounds

Yıl 2024, Cilt: 14 Sayı: 2, 29 - 49, 31.12.2024

Gamze Özgül Artuç

https://doi.org/10.37094/adyujsci.1572580

Öz

Coumarins and their derivatives, which are secondary metobalites of many plants, are heterocyclic bioactive compounds with various biological properties. Due to these properties, the synthesis of various derivatives and the investigation of their properties are of great interest. 4-(chloromethyl)-7-hydroxy-5-methyl coumarin (1), 4-(chloromethyl)-7-hydroxy-8-methyl coumarin (2), and 4-(chloromethyl)-7-hydroxy coumarin (3) synthesized by Pechmann condensation reaction and characterized by FT-IR, NMR spectral data and elemental analysis data. The antioxidant capacities of the compounds were investigated by difhenyl-2-picrylhydrazyl (DPPH) radical scavenger assay using the UV-Vis spectrophotometric method. The interactions of the compounds with ROS-producing cytochrome P-450, xanthine oxidase, lipooxygenase, monoamine oxidase, and nicotinamide adenine dinucleotide phosphate oxidase enzymes were investigated by molecular docking. All compounds interacted well in the active binding site of most of the enzymes (about 6-8 kcal/mol). The pharmacokinetic and toxicokinetic properties of the compounds, indicating their potential as drug candidates, were analyzed by ADMET predictions. All the results obtained showed that the compounds have properties that could be drug candidates.

Anahtar Kelimeler

Coumarin, antioxidant, molecular docking, ADMET

Bazı 4-klorometil Substitüe Kumarin Bileşiklerinin DPPH Antioksidan Deneyleri, Moleküler Kenetlenme Çalışmaları ve ADMET Tahminleri

Öz

Birçok bitkinin ikincil metobalitleri olan kumarinler ve türevleri, çeşitli biyolojik özelliklere sahip heterosiklik biyoaktif bileşiklerdir. Bu özelliklerinden dolayı çeşitli türevlerinin sentezi ve özelliklerinin araştırılması oldukça ilgi çekicidir. 4-(klorometil)-7-hidroksi-5-metil kumarin (1), 4-(klorometil)-7-histoksi-8-metil kumarin (2) ve 4-(klorometil)-7-hidroksi kumarin (3) Pechmann kondenzasyon reaksiyonu ile sentezlenmiş ve FT-IR, NMR spektrumları ve elementel analiz ile karakterize edilmiştir. Bileşiklerin antioksidant kapasiteleri UV-Vis spektrofotometrik yöntemi kullanılarak difenil-2-pikrilhidrazil (DPPH) radikal süpürme deneyleri ile araştırılmıştır. Moleküler yerleştirme ile bileşiklerin, ROS üreten enzimler sitokrom P-450, ksantin oksidaz, lipooksijenaz, monoamin oksidaz ve nikotinamid adenin dinükleotit fosfat oksidaz enzimleri ile etkileşimleri incelenmiştir. Tüm bileşikler enzimlerin aktif bölgeleriyle iyi etkileşim göstermiştir (about 6-8 kcal/mol). Bileşiklerin farmakokinetik ve toksikokinetik özellikleri, ilaç adayı olabilme potansiyelleri ADMET tahminleri yapılarak incelenmiştir. Tüm sonuçlar bileşiklerin, ilaç adayı olma potansiyellerine sahip özelliklere sahip bileşikler olduklarını göstermiştir.

Anahtar Kelimeler

Kumarin, Antioksidan, Moleküler yerleştirme, ADMET

Kaynakça

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