Pharmacophore elucidation of phosphoiodyn A - Potent and selective peroxisome proliferator-activated receptor β/δ agonists with neuroprotective activity

Nihar Kinarivala, Ji Ho Suh, Mina Botros, Paul Webb, Paul C. Trippier

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

We report the pharmacophore of the peroxisome proliferator-activated receptor δ (PPARδ) agonist natural product phosphoiodyn A is the phosphonate core. Synthesis of simplified phosphonate esters 13 and 15 provide structurally novel, highly selective and potent PPARδ agonists (EC50 =78 and 112nM, respectively). Further, both compounds demonstrate significant neuroprotective activity in an in vitro cellular model indicating that phosphonates may be an effective novel scaffold for the design of therapeutics for the treatment of neurodegenerative disorders.

Original languageEnglish (US)
JournalBioorganic and Medicinal Chemistry Letters
DOIs
StateAccepted/In press - Jan 8 2016

Keywords

  • BJWXRQUITKSDPA-UHFFFAOYSA-N
  • KXXHZVHYFQSELL-UHFFFAOYSA-N
  • Neurodegeneration
  • Neuroprotection
  • Pharmacophore identification
  • PPAR agonist
  • SEHJHHHUIGULEI-UHFFFAOYSA-N

ASJC Scopus subject areas

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

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