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

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 p...

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Autores principales: Zhu, Ruixin, Hu, Liwei, Li, Haiyun, Su, Juan, Cao, Zhiwei, Zhang, Weidong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Molecular Diversity Preservation International (MDPI) 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3116189/
https://www.ncbi.nlm.nih.gov/pubmed/21686183
http://dx.doi.org/10.3390/ijms12053250
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author Zhu, Ruixin
Hu, Liwei
Li, Haiyun
Su, Juan
Cao, Zhiwei
Zhang, Weidong
author_facet Zhu, Ruixin
Hu, Liwei
Li, Haiyun
Su, Juan
Cao, Zhiwei
Zhang, Weidong
author_sort Zhu, Ruixin
collection PubMed
description 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.
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spelling pubmed-31161892011-06-16 Novel Natural Inhibitors of CYP1A2 Identified by in Silico and in Vitro Screening Zhu, Ruixin Hu, Liwei Li, Haiyun Su, Juan Cao, Zhiwei Zhang, Weidong Int J Mol Sci Article 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. Molecular Diversity Preservation International (MDPI) 2011-05-18 /pmc/articles/PMC3116189/ /pubmed/21686183 http://dx.doi.org/10.3390/ijms12053250 Text en © 2011 by the authors; licensee MDPI, Basel, Switzerland. http://creativecommons.org/licenses/by/3.0 This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Article
Zhu, Ruixin
Hu, Liwei
Li, Haiyun
Su, Juan
Cao, Zhiwei
Zhang, Weidong
Novel Natural Inhibitors of CYP1A2 Identified by in Silico and in Vitro Screening
title Novel Natural Inhibitors of CYP1A2 Identified by in Silico and in Vitro Screening
title_full Novel Natural Inhibitors of CYP1A2 Identified by in Silico and in Vitro Screening
title_fullStr Novel Natural Inhibitors of CYP1A2 Identified by in Silico and in Vitro Screening
title_full_unstemmed Novel Natural Inhibitors of CYP1A2 Identified by in Silico and in Vitro Screening
title_short Novel Natural Inhibitors of CYP1A2 Identified by in Silico and in Vitro Screening
title_sort novel natural inhibitors of cyp1a2 identified by in silico and in vitro screening
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3116189/
https://www.ncbi.nlm.nih.gov/pubmed/21686183
http://dx.doi.org/10.3390/ijms12053250
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