Next Article in Journal
Microfluidic Mixing: A Review
Previous Article in Journal
Mechanism of Sphingosine 1-Phosphate- and Lysophosphatidic Acid-Induced Up-Regulation of Adhesion Molecules and Eosinophil Chemoattractant in Nerve Cells
Article Menu

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2011, 12(5), 3250-3262;

Novel Natural Inhibitors of CYP1A2 Identified by in Silico and in Vitro Screening

Department of Natural Medicinal Chemistry, School of Pharmacy, Second Military Medical University, Shanghai 200433, China
School of Life Sciences and Technology, Tongji University, 1239 Siping Road, Shanghai 200092, China
Shanghai Center for Bioinformation Technology, 100 Qinzhou Road, Shanghai 200235, China
School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200030, China
Authors to whom correspondence should be addressed.
Received: 4 March 2011 / Revised: 6 May 2011 / Accepted: 9 May 2011 / Published: 18 May 2011
(This article belongs to the Section Biochemistry)
Full-Text   |   PDF [343 KB, uploaded 19 June 2014]   |  


Inhibition of cytochrome P450 (CYP) is a major cause of herb–drug interactions. The CYP1A2 enzyme plays a major role in the metabolism of drugs in humans. Its broad substrate specificity, as well as its inhibition by a vast array of structurally diverse herbal active ingredients, has indicated the possibility of metabolic herb–drug interactions. Therefore nowadays searching inhibitors for CYP1A2 from herbal medicines are drawing much more attention by biological, chemical and pharmological scientists. In our work, a pharmacophore model as well as the docking technology is proposed to screen inhibitors from herbal ingredients data. Firstly different pharmaphore models were constructed and then validated and modified by 202 herbal ingredients. Secondly the best pharmaphore model was chosen to virtually screen the herbal data (a curated database of 989 herbal compounds). Then the hits (147 herbal compounds) were continued to be filtered by a docking process, and were tested in vitro successively. Finally, five of eighteen candidate compounds (272, 284, 300, 616 and 817) were found to have inhibition of CYP1A2 activity. The model developed in our study is efficient for in silico screening of large herbal databases in the identification of CYP1A2 inhibitors. It will play an important role to prevent the risk of herb–drug interactions at an early stage of the drug development process. View Full-Text
Keywords: CYP1A2; pharmacophore; docking; herb–drug interaction CYP1A2; pharmacophore; docking; herb–drug interaction

Graphical abstract

This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

Supplementary material


Share & Cite This Article

MDPI and ACS Style

Zhu, R.; Hu, L.; Li, H.; Su, J.; Cao, Z.; Zhang, W. Novel Natural Inhibitors of CYP1A2 Identified by in Silico and in Vitro Screening. Int. J. Mol. Sci. 2011, 12, 3250-3262.

Show more citation formats Show less citations formats

Related Articles

Article Metrics

Article Access Statistics



[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top