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

2 Citations (Scopus)

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 112 nM, 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)
Pages (from-to)1889-1893
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume26
Issue number8
DOIs
StatePublished - Apr 15 2016

Fingerprint

Organophosphonates
Peroxisome Proliferator-Activated Receptors
Biological Products
Scaffolds
Neurodegenerative Diseases
Esters
phosphoiodyn A
Therapeutics

Keywords

  • Neurodegeneration
  • Neuroprotection
  • PPAR agonist
  • Pharmacophore identification

ASJC Scopus subject areas

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

Cite this

Pharmacophore elucidation of phosphoiodyn A - Potent and selective peroxisome proliferator-activated receptor β/δ agonists with neuroprotective activity. / Kinarivala, Nihar; Suh, Ji Ho; Botros, Mina; Webb, Paul; Trippier, Paul C.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 26, No. 8, 15.04.2016, p. 1889-1893.

Research output: Contribution to journalArticle

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