Accession number:20094012363766
Title: Computational screening and design of traditional Chinese medicine (TCM) to block phosphodiesterase-5
Authors: Chen, Calvin Yu-Chian (1)
Author affiliation:(1) Laboratory of Pharmacoinformatics and Nanotechnology, School of Chinese Medicine, China Medical University, Taichung, 40402, Taiwan; (2) Department of Bioinformatics, Asia University, Taichung, 41354, Taiwan Corresponding author:Chen, C.Y.-C.
Source title: Journal of Molecular Graphics and Modelling Abbreviated source title:J. Mol. Graph. Model.
Volume:28 Issue:3
Issue date:October 2009 Publication year:2009 Pages:261-269
Language:English ISSN:10933263 CODEN:JMGMFI
Document type:Journal article (JA)
Publisher:Elsevier Inc., 360 Park Avenue South, New York, NY 10010, United States
Abstract:The traditional Chinese medicines (TCM), Epimedium sagittatum (ESs), Cnidium monnieri (CMs), and Semen cuscutae (SCs), were used for treating erectile dysfunction since the ancient Han dynasty (202 BC-AD 220). Phosphodiesterase-5 (PDE-5) is
deemed the target protein for inhibition to treat erectile dysfunction.
In this study, a reliable multiple linear regression (MLR) model (r value = 0.8484) was used to predict the activities of new candidates which were designed from ES, CM, and SC. From docking and
pharmacophore analysis, the potent candidates among ES, CM, and SC were screened. SC01, SC03, and ES03b were predicted to have high potencies based on MLR analysis and high docking scores.
Additionally, from our analysis, we make the follow conclusion (1) Hydrophobic compounds tend to be more potent PDE-5 inhibitors;
(2) Because of the big binding site, inhibitors with molecular weights
over 500 remain potent; (3) From the pharmacophore analysis, the features of hydrogen bond acceptors are the basis for designing novel inhibitors of PDE-5 and (4) According to MLR analysis, the number of ring groups could be up to 6, but the number of aromatic rings was limited to 4 to be potent. This study offers an alternative way to screen PDE-5 inhibitors from TCM and provides a scientific basis for confirming pharmacological actions of TCM. © 2009 Elsevier Inc. All rights reserved.
Number of references:29 Main heading:Medicine
Controlled terms: Agricultural products - Aircraft engines - Binding energy - Binding sites - Docking - Enzyme inhibition - Hydrogen - Hydrogen bonds - Hydrophobicity - Linear regression - Partial differential equations - Pharmacodynamics
Uncontrolled terms: Erectile dysfunction - Multiple linear regressions (MLR) - Pharmacophore analysis - Phosphodiesterase-5 (PDE-5) - Traditional Chinese medicines (TCM)
Classification code:931.2 Physical Properties of Gases, Liquids and Solids - 801.2 Biochemistry - 801.4 Physical Chemistry - 804
Chemical Products Generally - 821.4 Agricultural Products - 921.2 Calculus - 922.2 Mathematical Statistics - 801 Chemistry - 672 Naval Vessels - 655.1 Spacecraft, General - 653.1 Aircraft Engines, General - 461.8 Biotechnology - 461.6 Medicine and Pharmacology - 674.1 Small Marine Craft
DOI:10.1016/j.jmgm.2009.08.004 Database:Compendex
Compilation and indexing terms, Copyright 2009 Elsevier Inc.
