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Title: Chemical synthesis and biological evaluation of ω-hydroxy polyunsaturated fatty acids.

Authors: Hwang, Sung Hee; Wagner, Karen; Xu, Jian; Yang, Jun; Li, Xichun; Cao, Zhengyu; Morisseau, Christophe; Lee, Kin Sing Stephen; Hammock, Bruce D

Published In Bioorg Med Chem Lett, (2017 Feb 01)

Abstract: ω-Hydroxy polyunsaturated fatty acids (PUFAs), natural metabolites from arachidonic acid (ARA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were prepared via convergent synthesis approach using two key steps: Cu-mediated CC bond formation to construct methylene skipped poly-ynes and a partial alkyne hydrogenation where the presence of excess 2-methyl-2-butene as an additive that is proven to be critical for the success of partial reduction of the poly-ynes to the corresponding cis-alkenes without over-hydrogenation. The potential biological function of ω-hydroxy PUFAs in pain was evaluated in naive rats. Following intraplantar injection, 20-hydroxyeicosatetraenoic acid (20-HETE, ω-hydroxy ARA) generated an acute decrease in paw withdrawal thresholds in a mechanical nociceptive assay indicating pain, but no change was observed from rats which received either 20-hydroxyeicosapentaenoic acid (20-HEPE, ω-hydroxy EPA) or 22-hydroxydocosahexaenoic acid (22-HDoHE, ω-hydroxy DHA). We also found that both 20-HEPE and 22-HDoHE are more potent than 20-HETE to activate murine transient receptor potential vanilloid receptor1 (mTRPV1).

PubMed ID: 28025003 Exiting the NIEHS site

MeSH Terms: Analgesics/chemical synthesis*; Analgesics/chemistry; Analgesics/therapeutic use; Animals; Eicosapentaenoic Acid/metabolism; Fatty Acids, Unsaturated/chemical synthesis; Fatty Acids, Unsaturated/chemistry; Fatty Acids, Unsaturated/therapeutic use; Hydroxyeicosatetraenoic Acids/therapeutic use; Pain Threshold; Pain/drug therapy; Rats; Transient Receptor Potential Channels/agonists; Transient Receptor Potential Channels/metabolism

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