PMID- 19747866
OWN - NLM
STAT- MEDLINE
DCOM- 20091211
LR  - 20101118
IS  - 1873-4243 (Electronic)
IS  - 1093-3263 (Linking)
VI  - 28
IP  - 3
DP  - 2009 Oct
TI  - Computational screening and design of traditional Chinese medicine (TCM) to block 
      phosphodiesterase-5.
PG  - 261-9
LID - 10.1016/j.jmgm.2009.08.004 [doi]
AB  - 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.
FAU - Chen, Calvin Yu-Chian
AU  - Chen CY
AD  - Laboratory of Pharmacoinformatics and Nanotechnology, School of Chinese Medicine, 
      China Medical University, Taichung, 40402, Taiwan, ROC. ycc@mail.cmu.edu.tw
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090808
PL  - United States
TA  - J Mol Graph Model
JT  - Journal of molecular graphics & modelling
JID - 9716237
RN  - 0 (Drugs, Chinese Herbal)
RN  - 0 (Phosphodiesterase 5 Inhibitors)
SB  - IM
MH  - Cnidium/chemistry
MH  - Drugs, Chinese Herbal/*pharmacology
MH  - Epimedium/chemistry
MH  - Erectile Dysfunction/drug therapy
MH  - Humans
MH  - Linear Models
MH  - Male
MH  - Medicine, Chinese Traditional/*methods
MH  - Molecular Structure
MH  - *Phosphodiesterase 5 Inhibitors
EDAT- 2009/09/15 06:00
MHDA- 2009/12/16 06:00
CRDT- 2009/09/15 06:00
PHST- 2009/04/09 00:00 [received]
PHST- 2009/07/31 00:00 [revised]
PHST- 2009/08/03 00:00 [accepted]
PHST- 2009/09/15 06:00 [entrez]
PHST- 2009/09/15 06:00 [pubmed]
PHST- 2009/12/16 06:00 [medline]
AID - S1093-3263(09)00084-9 [pii]
AID - 10.1016/j.jmgm.2009.08.004 [doi]
PST - ppublish
SO  - J Mol Graph Model. 2009 Oct;28(3):261-9. doi: 10.1016/j.jmgm.2009.08.004. Epub 
      2009 Aug 8.