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Discovery of Novel Soluble Epoxide Hydrolase Inhibitors as Potent Vasodilators
In view of the role of sEH (soluble epoxide hydrolase) in hypertension, we have developed a rigorously validated pharmacophore model containing one HBA (Hydrogen Bond Acceptor), two HY (Hydrophobic) and one RA (Ring Aromatic) features. The model was used as a query to search the NCI (National Cancer...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6168526/ https://www.ncbi.nlm.nih.gov/pubmed/30279487 http://dx.doi.org/10.1038/s41598-018-32449-4 |
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author | Tripathi, Neetika Paliwal, Sarvesh Sharma, Swapnil Verma, Kanika Gururani, Ritika Tiwari, Akanksha Verma, Amrita Chauhan, Monika Singh, Aarti Kumar, Dipak Pant, Aditya |
author_facet | Tripathi, Neetika Paliwal, Sarvesh Sharma, Swapnil Verma, Kanika Gururani, Ritika Tiwari, Akanksha Verma, Amrita Chauhan, Monika Singh, Aarti Kumar, Dipak Pant, Aditya |
author_sort | Tripathi, Neetika |
collection | PubMed |
description | In view of the role of sEH (soluble epoxide hydrolase) in hypertension, we have developed a rigorously validated pharmacophore model containing one HBA (Hydrogen Bond Acceptor), two HY (Hydrophobic) and one RA (Ring Aromatic) features. The model was used as a query to search the NCI (National Cancer Institute) and Maybridge database leading to retrieval of many compounds which were sorted on the basis of predicted activity, fit value and Lipinski’s violation. The selected compounds were docked into the active site of enzyme soluble epoxide hydrolase. Potential interactions were observed between the features of the identified hits and the amino acids present in the docking site. The three selected compounds were subjected to in vitro evaluation using enzyme- based assay and the isolated rat aortic model followed by cytotoxicity studies. The results demonstrate that the identified compounds are potent, safe and novel soluble epoxide hydrolase inhibitors. |
format | Online Article Text |
id | pubmed-6168526 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-61685262018-10-05 Discovery of Novel Soluble Epoxide Hydrolase Inhibitors as Potent Vasodilators Tripathi, Neetika Paliwal, Sarvesh Sharma, Swapnil Verma, Kanika Gururani, Ritika Tiwari, Akanksha Verma, Amrita Chauhan, Monika Singh, Aarti Kumar, Dipak Pant, Aditya Sci Rep Article In view of the role of sEH (soluble epoxide hydrolase) in hypertension, we have developed a rigorously validated pharmacophore model containing one HBA (Hydrogen Bond Acceptor), two HY (Hydrophobic) and one RA (Ring Aromatic) features. The model was used as a query to search the NCI (National Cancer Institute) and Maybridge database leading to retrieval of many compounds which were sorted on the basis of predicted activity, fit value and Lipinski’s violation. The selected compounds were docked into the active site of enzyme soluble epoxide hydrolase. Potential interactions were observed between the features of the identified hits and the amino acids present in the docking site. The three selected compounds were subjected to in vitro evaluation using enzyme- based assay and the isolated rat aortic model followed by cytotoxicity studies. The results demonstrate that the identified compounds are potent, safe and novel soluble epoxide hydrolase inhibitors. Nature Publishing Group UK 2018-10-02 /pmc/articles/PMC6168526/ /pubmed/30279487 http://dx.doi.org/10.1038/s41598-018-32449-4 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Tripathi, Neetika Paliwal, Sarvesh Sharma, Swapnil Verma, Kanika Gururani, Ritika Tiwari, Akanksha Verma, Amrita Chauhan, Monika Singh, Aarti Kumar, Dipak Pant, Aditya Discovery of Novel Soluble Epoxide Hydrolase Inhibitors as Potent Vasodilators |
title | Discovery of Novel Soluble Epoxide Hydrolase Inhibitors as Potent Vasodilators |
title_full | Discovery of Novel Soluble Epoxide Hydrolase Inhibitors as Potent Vasodilators |
title_fullStr | Discovery of Novel Soluble Epoxide Hydrolase Inhibitors as Potent Vasodilators |
title_full_unstemmed | Discovery of Novel Soluble Epoxide Hydrolase Inhibitors as Potent Vasodilators |
title_short | Discovery of Novel Soluble Epoxide Hydrolase Inhibitors as Potent Vasodilators |
title_sort | discovery of novel soluble epoxide hydrolase inhibitors as potent vasodilators |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6168526/ https://www.ncbi.nlm.nih.gov/pubmed/30279487 http://dx.doi.org/10.1038/s41598-018-32449-4 |
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