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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...

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Autores principales: Tripathi, Neetika, Paliwal, Sarvesh, Sharma, Swapnil, Verma, Kanika, Gururani, Ritika, Tiwari, Akanksha, Verma, Amrita, Chauhan, Monika, Singh, Aarti, Kumar, Dipak, Pant, Aditya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
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.
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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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