In Silico Studies of Two Biphenyl Based Oxime Containing Ligands

Abstract

Two biphenyl based ligands were tested for their molecular docking, ADME and toxicity properties in silico. Molecular docking studies performed with two factors (VEGFR-2 and EGFRK) which are known to be effective in tumor growth. Two ligands were similar in structure except one atom difference between ligands which is H and Cl. This small difference made an important impact on the molecular docking energy scores of ligand protein couples. The Cl atom containing ligand-protein complexes showed drastically elevated energy levels which might be due to higher electronegativity of Cl atom. ADME properties of two ligands were also alike except a few parameters as the inhibition of two conjugation enzymes (CYP2C19 ve CYP2C9). The biggest difference shown by the ligands were the elimination of carcinogenicity and mutagenicity of H containing ligand by Cl atom containing ligand. Druglikeness of two biphenyl based oxime containing ligands was also tested and the results of a single atom exchange were evaluated in terms of new drug design and discovery.

Keywords

• : In Silico study
• Molecular docking
• ADMET
• Druglikeness

Oksim İçeren Bifenil Temelli İki Ligandın in silico Çalışmaları

Abstract

İki bifenil temelli ligandın moleküler kenetlenme, ADME ve toksisite özellikleri in silico olarak incelendi. Moleküler kenetlenme çalışmaları, tümör büyümesinde etkili olduğu bilinen iki faktör (VEGFR-2 ve EGFRK) kullanılarak gerçekleştirildi. İki ligand, H ve Cl olan bir atom farkı dışında yapısal açıdan benzer olarak seçildi. Bu küçük fark, ligand protein çiftlerinin moleküler kenetlenme enerji değerleri üzerinde önemli bir etki meydana getirdi. Cl atomu içeren ligand-protein kompleksleri, Cl atomunun daha yüksek elektronegatifliğinden kaynaklanabilecek büyük enerji değerlerine sahip olarak bulundu. İki konjugasyon enziminin (CYP2C19 ve CYP2C9) inhibisyonu gibi birkaç parametre dışında iki ligandın ADME özelliklerinin benzer olduğu belirlendi. Ligandların gösterdiği en büyük farkın, H içeren ligandın kanserojenliğinin ve mutajenitesinin Cl atomu içeren ligand ile ortadan kaldırması olduğu tespit edildi. İki bifenil bazlı oksim içeren ligandın ilaç benzerliği de test edildi ve tek bir atom değişiminin sonuçları, yeni ilaç tasarımı ve keşfi açısından değerlendirildi.

Keywords

• In silico çalışma
• Moleküler kenetlenme
• ADMET
• İlaçbenzerlik

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