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

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.

• Authors: Gabriella Spengler, Imre Ocsovszki, Ádám Szabó Tönki, Ryosuke Saijo, Genki Watanabe, Masami Kawase, Joseph Molnár
• Journal: Anticancer research (Anticancer Res) Vol. 35 Issue 11 Pg. 5915-9 (Nov 2015) ISSN: 1791-7530 [Electronic] Greece
• PMID: 26504015 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Chemical References

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

Topics

• 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, pharmacology)
• Humans
• Hydrocarbons, Fluorinated (chemistry, pharmacology)
• Lymphoma, T-Cell (drug therapy, pathology)
• Mice
• Phosphorus (chemistry)
• Tumor Cells, Cultured
• Vasodilator Agents (pharmacology)
• Verapamil (pharmacology)