1st International and 10th National Iranian Conference on Bioinformatics
Home Accepted Papers
Pharmacoinformatics Study and High-Throughput Virtual Screening to Discover Effective Natural Compounds in Treatment of Erectile Dysfunction
Paper ID : 1361-ICB10
Authors:
Fatemeh Nabizadeh *1, Farshad Qalekhani2
1Medical Biology Research Center, Health Technologies Institute, Kermanshah University of Medical Sciences(KUMS), Kermanshah 6714415185, Iran
2Pharmaceutical Sciences Research Center, Health Technologies Institute, Kermanshah University of Medical Sciences (KUMS), Kermanshah 6734667149, Iran
Abstract:
Erectile dysfunction (ED) is the consistent or recurrent inability to achieve and/or maintain penile erection sufficient for a satisfying sexual performance. It is expected that ≈322 million men worldwide will suffer from ED by 2025. Phosphodiesterase 5 (PDE5) is a well-studied enzyme that specifically targets cGMP produced by nitric oxide-mediated activation of the guanylyl cyclase. Considering the crucial function of cGMP generated through the activation of this signaling pathway in several physiological processes, pharmacological inhibition of PDE5 has been revealed to be beneficial in ED treatment. Sildenafil was the first PDE5 inhibitor that showed a wonderful efficacy in ED, but it can still cause several side effects. Here, we used a library of 1228 purchasable natural products to investigate their inhibitory effect on PDE5 through bioinformatics tools and databases. Primarily, the three-dimensional structure of PDE5 was downloaded from the "Protein Data Bank" database, containing the crystal structure of the enzyme together with its inhibitor, Sildenafil. Structure preparation for docking was performed using the UCSF Chimera program, and ADT software. Water molecules and Sildenafil were removed, and hydrogens were added to the structure. Then, docking between Sildenafil and PDE5 was performed using AutoDock Vina software, to validate the grid box and determine the positive control binding energy. Docking between PDE5 and the library of natural compounds was carried out by AutoDock Vina software on the MTiOpenScreen server. The top 20 compounds were later evaluated by the Lipinski rule, and five compounds that followed the rule were assessed for toxicity. Finally, Alpha-Spinasterol glucoside (Affinity = -11.1 (kcal/mol)) and Yuccagenin (Affinity = -11 (kcal/mol)) were chosen as the leading compounds, and the ADME properties of them were evaluated through the pkCSM server. After pharmacokinetics studies, we concluded that Alpha-Spinasterol glucoside and Yuccagenin as PDE5 inhibitors can be candidates for the treatment of ED.
Keywords:
Alpha-Spinasterol glucoside; Erectile dysfunction; Phosphodiesterase 5; Sildenafil; Yuccagenin.
Status : Paper Accepted (Poster Presentation)