Fluorinated β-Diketo Phosphorus Ylides Are Novel Inhibitors of the ABCB1 Efflux Pump of Cancer Cells.
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.
Department of Medical Microbiology and Immunobiology, Faculty of Medicine, University of Szeged, Szeged, Hungary.
Gabriella
G
Spengler
Department of Biochemistry, Faculty of Medicine, University of Szeged, Szeged, Hungary.
Imre
I
Ocsovszki
Department of Medical Microbiology and Immunobiology, Faculty of Medicine, University of Szeged, Szeged, Hungary.
Ádám Szabó
ÁS
Tönki
Faculty of Pharmaceutical Sciences, Matsuyama University, Ehime, Japan.
Ryosuke
R
Saijo
Faculty of Pharmaceutical Sciences, Matsuyama University, Ehime, Japan.
Genki
G
Watanabe
Faculty of Pharmaceutical Sciences, Matsuyama University, Ehime, Japan kawase@cc.matsuyama-u.ac.jp.
Masami
M
Kawase
Department of Medical Microbiology and Immunobiology, Faculty of Medicine, University of Szeged, Szeged, Hungary.
Joseph
J
Molnár
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000037:antagonists & inhibitors; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects*; D018432:Drug Resistance, Multiple / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005434:Flow Cytometry; D006571:Heterocyclic Compounds / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000737:chemistry / Q000494:pharmacology*; D016399:Lymphoma, T-Cell / Q000188:drug therapy* / Q000473:pathology*; D051379:Mice; D010758:Phosphorus / Q000737:chemistry*; D014407:Tumor Cells, Cultured; D014665:Vasodilator Agents / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D006571:Heterocyclic Compounds; D006845:Hydrocarbons, Fluorinated; D014665:Vasodilator Agents; D010758:Phosphorus; D014700:Verapamil
ABCB1; Multidrug resistance; P-glycoprotein; mouse T-lymphoma; phosphorus ylide; trifluoroacetyl