氟化β-二酮磷叶立德是癌细胞ABCB1外排泵的新型抑制剂。

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

作者信息

Spengler Gabriella, Ocsovszki Imre, Tönki Ádám Szabó, Saijo Ryosuke, Watanabe Genki, Kawase Masami, Molnár Joseph

机构信息

Department of Medical Microbiology and Immunobiology, Faculty of Medicine, University of Szeged, Szeged, Hungary.

Department of Biochemistry, Faculty of Medicine, University of Szeged, Szeged, Hungary.

出版信息

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

PMID:26504015

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.

摘要

外排泵抑制剂是一类能够逆转癌细胞多药耐药性（MDR）的有吸引力的化合物。在本研究中，基于10种磷叶立德（P-叶立德）对人ATP结合盒亚家族B成员1（ABCB1；P-糖蛋白）基因转染的L5178Y小鼠T淋巴瘤细胞的MDR逆转活性进行了比较。其中，三种磷叶立德，即三苯基膦亚基三氟乙酰基苯甲酰甲烷（Ph3P=C(COCF3)COPh）、三苯基膦亚基五氟丙酰基苯甲酰甲烷（Ph3P=C(COC2F5)COPh）和三苯基膦亚基七氟丁酰基苯甲酰甲烷（Ph3P=C(COC3F7)COPh）被鉴定为可选择性调节ABCB1泵。这些化合物对小鼠T淋巴瘤细胞具有低细胞毒性，其效力比阳性对照ABCB1抑制剂维拉帕米更强。