Discovery of Specific Inhibitors for Intestinal E. coli β-Glucuronidase through In Silico Virtual Screening
Joint Authors
Cheng, Ta-Chun
Chuang, Kuo-Hsiang
Roffler, Steve R.
Cheng, Kai-Wen
Leu, Yu-Lin
Chuang, Chih-Hung
Huang, Chien-Chaio
Kao, Chien-Han
Hsieh, Yuan-Chin
Cheng, Tian-Lu
Chen, Chien-Shu
Chang, L. S.
Source
Issue
Vol. 2015, Issue 2015 (31 Dec. 2015), pp.1-8, 8 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2015-03-09
Country of Publication
Egypt
No. of Pages
8
Main Subjects
Medicine
Information Technology and Computer Science
Abstract EN
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 β-glucuronidase (eβG) has been considered pivotal to colorectal carcinogenesis.
Specific inhibition of eβG may prevent reactivating the glucuronide-carcinogen and protect the intestine from ROS-mediated carcinogenesis.
In order to develop specific eβG inhibitors, we found that 59 candidate compounds obtained from the initial virtual screening had high inhibition specificity against eβG but not human βG.
In particular, we found that compounds 7145 and 4041 with naphthalenylidene-benzenesulfonamide (NYBS) are highly effective and selective to inhibit eβG activity.
Compound 4041 (IC50=2.8 μM) shows a higher inhibiting ability than compound 7145 (IC50=31.6 μM) against eβG.
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 eβG via hydrogen-bonding interactions.
These novel NYBS-based eβG specific inhibitors may provide as novel candidate compounds, which specifically inhibit eβG to reduce eβG-based carcinogenesis and intestinal injury.
American Psychological Association (APA)
Cheng, Ta-Chun& Chuang, Kuo-Hsiang& Roffler, Steve R.& Cheng, Kai-Wen& Leu, Yu-Lin& Chuang, Chih-Hung…[et al.]. 2015. Discovery of Specific Inhibitors for Intestinal E. coli β-Glucuronidase through In Silico Virtual Screening. The Scientific World Journal،Vol. 2015, no. 2015, pp.1-8.
https://search.emarefa.net/detail/BIM-1079075
Modern Language Association (MLA)
Cheng, Ta-Chun…[et al.]. Discovery of Specific Inhibitors for Intestinal E. coli β-Glucuronidase through In Silico Virtual Screening. The Scientific World Journal No. 2015 (2015), pp.1-8.
https://search.emarefa.net/detail/BIM-1079075
American Medical Association (AMA)
Cheng, Ta-Chun& Chuang, Kuo-Hsiang& Roffler, Steve R.& Cheng, Kai-Wen& Leu, Yu-Lin& Chuang, Chih-Hung…[et al.]. Discovery of Specific Inhibitors for Intestinal E. coli β-Glucuronidase through In Silico Virtual Screening. The Scientific World Journal. 2015. Vol. 2015, no. 2015, pp.1-8.
https://search.emarefa.net/detail/BIM-1079075
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1079075