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BioMed Research International
Volume 2014, Article ID 873010, 12 pages
http://dx.doi.org/10.1155/2014/873010
Research Article

Potential Smoothened Inhibitor from Traditional Chinese Medicine against the Disease of Diabetes, Obesity, and Cancer

1School of Pharmacy, China Medical University, Taichung 40402, Taiwan
2School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung 40402, Taiwan
3Department of Acupuncture, China Medical University Hospital, Taichung, Taiwan
4Research Center for Chinese Medicine & Acupuncture, China Medical University, Taichung, Taiwan
5Department of Biomedical Informatics, Asia University, Taichung 41354, Taiwan
6School of Medicine, College of Medicine, China Medical University, Taichung 40402, Taiwan
7Human Genetic Center, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan

Received 14 February 2014; Accepted 15 February 2014; Published 1 July 2014

Academic Editor: Chung Y. Hsu

Copyright © 2014 Kuan-Chung Chen et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Nowadays, obesity becomes a serious global problem, which can induce a series of diseases such as type 2 diabetes mellitus, cancer, cardiovascular disease, metabolic syndrome, and stoke. For the mechanisms of diseases, the hedgehog signaling pathway plays an important role in body patterning during embryogenesis. For this reason, smoothened homologue (Smo) protein had been indicated as the drug target. In addition, the small-molecule Smo inhibitor had also been used in oncology clinical trials. To improve drug development of TCM compounds, we aim to investigate the potent lead compounds as Smo inhibitor from the TCM compounds in TCM Database@Taiwan. The top three TCM compounds, precatorine, labiatic acid, and 2,2′-[benzene-1,4-diylbis(methanediyloxybenzene-4,1-diyl)]bis(oxoacetic acid), have displayed higher potent binding affinities than the positive control, LY2940680, in the docking simulation. After MD simulations, which can optimize the result of docking simulation and validate the stability of H-bonds between each ligand and Smo protein under dynamic conditions, top three TCM compounds maintain most of interactions with Smo protein, which keep the ligand binding stable in the binding domain. Hence, we propose precatorine, labiatic acid, and 2,2′-[benzene-1,4-diylbis(methanediyloxybenzene-4,1-diyl)]bis(oxoacetic acid) as potential lead compounds for further study in drug development process with the Smo protein.