Radwan Awwad Abdoh
King Saud University, College of Pharmacy, Department of Pharmaceutics, Riyadh 11451, Saudi Arabia ; Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt.
Bioinformation. 2015 Feb 28;11(2):63-6. doi: 10.6026/97320630011063. eCollection 2015.
cGMP-binding cGMP-specific PDE, PDE5 plays a key role in the hydrolysis of cyclic guanidine monophosphate. Because cGMP mediates vascular functions, a PDE5 inhibitor that elevates cGMP level is an attractive means for vasodilatation and treatment of erectile dysfunction. In this paper we report the elucidation of the common pharmacophore hypothesis of different classes of PDE5 inhibitors. Using LigandScout program, pharmacophore modelling studies were performed on prior reported potent PDE5 inhibitors with a variety of scaffolds in order to identify one common set of critical chemical features of these PDE5 inhibitors 1-52. The best pharmacophore model, model-1, characterized by four chemical features: one aromatic ring, one hydrophobe, one hydrogen acceptors and one hydrogen donor. Using Dock6 program, docking studies were performed in order to investigate the mode of binding of these compounds. The molecular docking study allowed confirming the preferential binding mode of different classes of PDE5 inhibitors inside the active site. The obtained binding mode was as same as that of vardenafil, X-ray ligand with different orientation with varied PDE5 inhibitors׳ scaffold.
环磷酸鸟苷（cGMP）结合型特异性cGMP磷酸二酯酶（PDE）5在环磷酸鸟苷的水解过程中起着关键作用。由于cGMP介导血管功能，一种能够提高cGMP水平的PDE5抑制剂是实现血管舒张和治疗勃起功能障碍的一种有吸引力的手段。在本文中，我们报告了不同类别的PDE5抑制剂共同药效团假说的阐明。使用LigandScout程序，对先前报道的具有各种支架结构的强效PDE5抑制剂进行了药效团建模研究，以确定这些PDE5抑制剂1 - 52的一组共同的关键化学特征。最佳药效团模型为模型-1，其具有四个化学特征：一个芳香环、一个疏水基团、一个氢键受体和一个氢键供体。使用Dock6程序进行对接研究，以研究这些化合物的结合模式。分子对接研究证实了不同类别的PDE5抑制剂在活性位点内的优先结合模式。所获得的结合模式与伐地那非相同，伐地那非是一种X射线配体，与不同的PDE5抑制剂支架结构具有不同的取向。
