Discovery of Novel Soluble Epoxide Hydrolase Inhibitors as Potent Vasodilators

Scientific Reports
Neetika TripathiAditya Pant

Abstract

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.

References

Aug 15, 1998·Archives of Biochemistry and Biophysics·C MorisseauB D Hammock
Aug 4, 1999·Proceedings of the National Academy of Sciences of the United States of America·C MorisseauB D Hammock
May 15, 2002·Biochemical Pharmacology·Christophe MorisseauBruce D Hammock
Mar 7, 2003·Journal of Medicinal Chemistry·Nathan R McElroyBruce D Hammock
Apr 12, 2005·Annual Review of Pharmacology and Toxicology·Christophe Morisseau, Bruce D Hammock
May 13, 2005·Journal of Medicinal Chemistry·In-Hae KimBruce D Hammock
Jul 5, 2005·Proceedings of the National Academy of Sciences of the United States of America·Kara R SchmelzerBruce D Hammock
Jul 28, 2006·Bioorganic & Medicinal Chemistry Letters·Paul D JonesBruce D Hammock
Dec 23, 2006·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Magali CordaillatBernard Jover
Jun 13, 2009·Bioorganic & Medicinal Chemistry Letters·Sampath-Kumar AnandanRichard D Gless
Nov 15, 2011·Bioorganic & Medicinal Chemistry Letters·Stevan PecicDonald W Landry
Dec 15, 2012·Bioorganic & Medicinal Chemistry Letters·Stevan PecicShi-Xian Deng

❮ Previous
Next ❯

Citations

Jun 3, 2020·Archiv der Pharmazie·Iman MahloojiSayyed Abbas Tabatabai
Nov 9, 2019·Journal of Biomolecular Structure & Dynamics·Sudha Bhagwati, Mohammad Imran Siddiqi
Dec 2, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Amarjyoti Das MahapatraBhaskar Datta
Jun 4, 2021·Drug Discovery Today·Maria BzówkaArtur Góra

❮ Previous
Next ❯

Software Mentioned

Discovery
Discovery Studio
ChemDraw Ultra
Studio
CHARMm
LibDock
AUDA

Related Concepts

Related Feeds

Antihypertensive Agents: Mechanisms of Action

Antihypertensive drugs are used to treat hypertension (high blood pressure) which aims to prevent the complications of high blood pressure, such as stroke and myocardial infarction. Discover the latest research on antihypertensive drugs and their mechanism of action here.