Molecular Docking and ADMET Profiling Studies of some Fluorinated Sulfonates and their Schiff Base Derivatives: Potential inhibitors of HMG-CoA Reductase

Yıl 2025, Cilt: 15 Sayı: 2 , 127 - 144 , 31.12.2025

Selami Ercan

https://doi.org/10.37094/adyujsci.1730312

https://izlik.org/JA46UH45NM

Öz

Hypercholesterolemia is one of the major risk factors of cardiovascular diseases. HMG-CoA reductase enzyme, the main drug target to reduce the cholesterol levels, catalyzes biosynthesis of cholesterol. In addition to in-silico estimations of ADMET profiles of compounds composed of several functional groups which are known to be effective for many diseases, a molecular docking study was performed to investigate binding modes of compounds in binding site of HMG-CoA reductase. Prior to docking studies, the RESP charges of compounds were defined by quantum mechanics calculations. Analyzes revealed that eleven Schiff base derivatives showed better binding rather than co-crystalized drug Rosuvastatin. Results demonstrated that Schiff base group included compounds have better inhibition effects on HMG-CoA reductase than their related pre-compounds. The docking scores of compounds range between -7.22 kcal/mol and -9.43 kcal/mol. The compounds L16, L28, and L15 were the ligands having best binding scores with the values -9.43 kcal/mol, -9.24 kcal/mol, and -9.23 kcal/mol, respectively. The analyses showed that compounds interact with several key residues of enzyme such as Glu559, Asp690, Lys691, Lys692, and Asp767.

Anahtar Kelimeler

Aryl sulfonates , Schiff bases , HMG-CoA reductase , ADMET , Molecular Docking

Bazı Florlu Sülfonatların ve Schiff Baz Türevlerinin Moleküler Yerleştirme ve ADMET Profilleme Çalışmaları: HMG-CoA Redüktazın Potansiyel İnhibitörleri

https://izlik.org/JA46UH45NM

Öz

Hiperkolesterolemi, kardiyovasküler hastalıkların başlıca risk faktörlerinden biridir. Kolesterol seviyelerini düşürmek için ana ilaç hedefi olan HMG-CoA redüktaz enzimi, kolesterolün biyosentezini katalize eder. Birçok hastalık için etkili olduğu bilinen çeşitli fonksiyonel gruplardan oluşan bileşiklerin ADMET profillerinin in silico tahminlerine ek olarak, HMG-CoA redüktazın bağlanma bölgesindeki bileşiklerin bağlanma modlarını araştırmak için moleküler yerleştirme çalışması yapıldı. Yerleştirme çalışmalarından önce, bileşiklerin RESP yükleri kuantum mekaniği hesaplamalarıyla tanımlandı. Analizler, on bir Schiff bazı türevinin ko-kristalize ilaç Rosuvastatin'den daha iyi bağlanma gösterdiğini ortaya koydu. Sonuçlar, Schiff bazı grubu içeren bileşiklerin, ilgili ön bileşiklere göre HMG-CoA redüktaz üzerinde daha iyi inhibisyon etkilerine sahip olduğunu gösterdi. Bileşiklerin yerleştirme puanları -7,22 kcal/mol ile -9,43 kcal/mol arasında değişmektedir. L16, L28 ve L15 bileşikleri sırasıyla -9,43 kcal/mol, -9,24 kcal/mol ve -9,23 kcal/mol değerleriyle en iyi bağlanma skorlarına sahip ligandlardı. Analizler bileşiklerin Glu559, Asp690, Lys691, Lys692 ve Asp767 gibi enzimin birkaç önemli kalıntısıyla etkileşime girdiğini gösterdi.

Anahtar Kelimeler

Aril sülfonatlar , Schiff bazları , HMG-CoA redüktaz , ADMET , Moleküler Yerleştirme

Kaynakça

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