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

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

Research output: Contribution to journalArticle

5 Citations (Scopus)

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 C[sbnd]C 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).

Original languageEnglish (US)
Pages (from-to)620-625
Number of pages6
JournalBioorganic and Medicinal Chemistry Letters
Volume27
Issue number3
DOIs
StatePublished - Feb 1 2017

Fingerprint

Unsaturated Fatty Acids
Hydroxy Acids
Eicosapentaenoic Acid
Hydrogenation
Docosahexaenoic Acids
Arachidonic Acid
Rats
TRPV Cation Channels
Pain
Acids
Alkynes
Alkenes
Metabolites
Assays
Injections
20-hydroxy-5,8,11,14-eicosatetraenoic acid

Keywords

  • 20-HEPE
  • 20-HETE
  • 22-HDoHE
  • Pain
  • TRPV1
  • ω-Hydroxy PUFA

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Cite this

Chemical synthesis and biological evaluation of ω-hydroxy polyunsaturated fatty acids. / Hwang, Sung Hee; Wagner, Karen; Xu, Jian; Yang, Jun; Li, Xichun; Cao, Zhengyu; Morisseau, Christophe; Lee, Kin Sing Stephen; Hammock, Bruce D.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 27, No. 3, 01.02.2017, p. 620-625.

Research output: Contribution to journalArticle

Hwang, SH, Wagner, K, Xu, J, Yang, J, Li, X, Cao, Z, Morisseau, C, Lee, KSS & Hammock, BD 2017, 'Chemical synthesis and biological evaluation of ω-hydroxy polyunsaturated fatty acids', Bioorganic and Medicinal Chemistry Letters, vol. 27, no. 3, pp. 620-625. https://doi.org/10.1016/j.bmcl.2016.12.002
Hwang, Sung Hee ; Wagner, Karen ; Xu, Jian ; Yang, Jun ; Li, Xichun ; Cao, Zhengyu ; Morisseau, Christophe ; Lee, Kin Sing Stephen ; Hammock, Bruce D. / Chemical synthesis and biological evaluation of ω-hydroxy polyunsaturated fatty acids. In: Bioorganic and Medicinal Chemistry Letters. 2017 ; Vol. 27, No. 3. pp. 620-625.
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