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The Scientific World Journal
Volume 2015 (2015), Article ID 740815, 8 pages
Research Article

Discovery of Specific Inhibitors for Intestinal E. coli  β-Glucuronidase through In Silico Virtual Screening

1Graduate Institute of Pharmacognosy, Taipei Medical University, 252 Wu Hsing Street, Taipei 11031, Taiwan
2Institute of Biomedical Sciences, Academia Sinica, 128 Section 2, Academia Road, Nankang, Taipei 11529, Taiwan
3Institute of Biomedical Science, 70 Lienhai Road, Kaohsiung 80424, National Sun Yat-Sen University, Taiwan
4Department of Pharmacy, Chia Nan University of Pharmacy and Science, 60 Section 1, Erh-Ren Road, Tainan 71710, Taiwan
5Department of Biomedical and Environmental Biology, Kaohsiung Medical University, 100 Shih-Chuan 1st Road, Kaohsiung 80708, Taiwan
6Graduate Institute of Medicine, Kaohsiung Medical University, 100 Shih-Chuan 1st Road, Kaohsiung 80708, Taiwan
7Center for Biomarkers and Biotech Drugs, Kaohsiung Medical University, 100 Shih-Chuan 1st Road, Kaohsiung 80708, Taiwan
8School of Pharmacy, China Medical University, 91 Hsueh-Shih Road, Taichung 40402, Taiwan

Received 15 August 2014; Accepted 27 August 2014

Academic Editor: Li-Yeh Chuang

Copyright © 2015 Ta-Chun Cheng 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.


Glucuronidation is a major metabolism process of detoxification for carcinogens, 4-(methylnitrosamino)-1-(3-pyridy)-1-butanone (NNK) and 1,2-dimethylhydrazine (DMH), of reactive oxygen species (ROS). However, intestinal E. coli   -glucuronidase (eG) has been considered pivotal to colorectal carcinogenesis. Specific inhibition of eG may prevent reactivating the glucuronide-carcinogen and protect the intestine from ROS-mediated carcinogenesis. In order to develop specific eG inhibitors, we found that 59 candidate compounds obtained from the initial virtual screening had high inhibition specificity against eG but not human G. In particular, we found that compounds 7145 and 4041 with naphthalenylidene-benzenesulfonamide (NYBS) are highly effective and selective to inhibit eG activity. Compound 4041  (μM) shows a higher inhibiting ability than compound 7145  (μM) against eG. Furthermore, the molecular docking analysis indicates that compound 4041 has two hydrophobic contacts to residues L361 and I363 in the bacterial loop, but 7145 has one contact to L361. Only compound 4041 can bind to key residue (E413) at active site of eG via hydrogen-bonding interactions. These novel NYBS-based eG specific inhibitors may provide as novel candidate compounds, which specifically inhibit eG to reduce eG-based carcinogenesis and intestinal injury.