N-oxide derivatives of 3-(3-pyridyl)-2-phosphonopropanoic acids as potential inhibitors of Rab geranylgeranylation

Xiang Zhou, Ella J. Born, Cheryl Allen, Sarah A. Holstein, David F. Wiemer

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Abstract The N-oxide derivatives of [2-(3-pyridinyl)-1-hydroxyethylidene-1,1-phosphonocarboxylic acid (or PEHPC) and [2-(3-pyridinyl)-1-ethylidene-1,1-phosphonocarboxylic acid (or PEPC) have been prepared and evaluated for their activity against several enzymes which utilize isoprenoids. The parent pyridines are known inhibitors of GGTase II, but the N-oxide derivatives show no improvement in biological activity in assays with the isolated enzyme. However, the PEHPC N-oxide did induce significant accumulation of intracellular light chain in myeloma cells, consistent with inhibition of Rab geranylgeranylation.

Original languageEnglish (US)
Article number22604
Pages (from-to)2331-2334
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume25
Issue number11
DOIs
StatePublished - Jun 1 2015

    Fingerprint

Keywords

  • Apoptosis
  • Bioassay
  • GGTase II
  • Myeloma
  • Pyridyl N-oxides
  • Rab GGTase

ASJC Scopus subject areas

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

Cite this