題名: Discovery of potent inhibitors for phosphodiesterase 5 by virtual screening and pharmacophore analysis
作者: Chen, CY (Chen, Chien-yu);Chang, YH (Chang, Yea-huey);Bau, DT (Bau, Da- tian);Huang, HJ (Huang, Hung-jin);Tsai, FJ (Tsai, Fuu-jen);Tsai, CH (Tsai, Chang-hai);Chen, CYC (Chen, Calvin Yu-chian)
貢獻者: Department of Bioinformatics
關鍵詞: phosphodiesterase5 (PDE5);Epimedium sagittatum;erectile dysfunction;pharmacophore analysis;quantitative structure- activity;relationship;PHARMACOINFORMATICS
APPROACH;DERIVATIVES;SUANZAOREN;PDE5;SILDENAFIL;RECEPTORS;LIGA NDS;AGONIST;BINDING;ASSAY
日期: 2009-08 上傳時
間:
2010-03-26T02:56:40Z
出版者: Asia University
摘要: Aim: To explore the potent inhibitor from one of the Traditional Chinese medicine (TCM), Epimedium sagittatum.
Methods: We predicted the potent compound, ES03b, de novo evolution from the four Epimedium sagittatum components were verified by
molecular docking, pharmacophore analysis, and analysis of quantitative structure-activity relationship (QSAR) model, which was constructed by multiple linear regression.
Results: ES03b was chosen to undergo drug modification via de novo evolution. By analyzing the pharmacophore features, we found that the hydrophobic core in the binding site and the hydrogen bond generated at Asn663 played key roles in designing PDE5 inhibitors. ES03b generated 49 diversities (Evo01-49). Evo48 had high activity in prediction. Although the value of prediction was overestimated, Evo48 was suggested as the potent lead.
Conclusion: In this study, we showed that the hydrophobic core in the binding site and hydrogen bond production on Asn663 played key roles to design PDE5 inhibitors. From several require validation analysis, Evo48 was suggested to be a potent inhibitor.
