Fluorinated β-Diketo Phosphorus Ylides Are Novel Inhibitors of the ABCB1 Efflux Pump of Cancer Cells

Anticancer Res. 2015 Nov;35(11):5915-9.

Abstract

Efflux pump inhibitors are attractive compounds that reverse multidrug resistance (MDR) in cancer cells. In the present study, 10 phosphorus ylides (P-ylides) were compared based on their MDR-reverting activity in human ATP-binding cassette sub-family B member 1 (ABCB1; P-glycoprotein) gene-transfected L5178Y mouse T-lymphoma cells. Among them, three P-ylides, Ph3P=C(COCF3)COPh, Ph3P=C(COC2F5)COPh and Ph3P=C(COC3F7)COPh were identified as selectively modulating the ABCB1 pump. These compounds, with low cytotoxicity against mouse T-lymphoma cells, exhibited more potency than the positive control ABCB1 inhibitor verapamil.

Keywords: ABCB1; Multidrug resistance; P-glycoprotein; mouse T-lymphoma; phosphorus ylide; trifluoroacetyl.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B / antagonists & inhibitors
  • Animals
  • Cell Proliferation / drug effects*
  • Drug Resistance, Multiple / drug effects
  • Drug Resistance, Neoplasm / drug effects
  • Flow Cytometry
  • Heterocyclic Compounds / chemistry
  • Heterocyclic Compounds / pharmacology*
  • Humans
  • Hydrocarbons, Fluorinated / chemistry
  • Hydrocarbons, Fluorinated / pharmacology*
  • Lymphoma, T-Cell / drug therapy*
  • Lymphoma, T-Cell / pathology*
  • Mice
  • Phosphorus / chemistry*
  • Tumor Cells, Cultured
  • Vasodilator Agents / pharmacology
  • Verapamil / pharmacology

Substances

  • ABCB1 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • Heterocyclic Compounds
  • Hydrocarbons, Fluorinated
  • Vasodilator Agents
  • Phosphorus
  • Verapamil