adyu j sci Adıyaman University Journal of Science 2147-1630 2146-586X Adıyaman Üniversitesi 10.37094/adyujsci.1730312 Molecular Docking Computational Chemistry Moleküler Yerleştirme Hesaplamalı Kimya Molecular Docking and ADMET Profiling Studies of some Fluorinated Sulfonates and their Schiff Base Derivatives: Potential inhibitors of HMG-CoA Reductase Bazı Florlu Sülfonatların ve Schiff Baz Türevlerinin Moleküler Yerleştirme ve ADMET Profilleme Çalışmaları: HMG-CoA Redüktazın Potansiyel İnhibitörleri https://orcid.org/0000-0002-9528-6122 Ercan Selami Batman University 12 31 2025 15 2 127 144 06 30 2025 12 14 2025 Copyright © 2011, Adıyaman Üniversitesi Fen Bilimleri Dergisi 2011 Adıyaman Üniversitesi Fen Bilimleri Dergisi

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.

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.

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