Thiorhodamines containing amide and thioamide functionality as inhibitors of the ATP-binding cassette drug transporter P-glycoprotein (ABCB1).
Thiorhodamines containing amide and thioamide functionality as inhibitors of the ATP-binding cassette drug transporter P-glycoprotein (ABCB1).
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DOI：
10.1016/j.bmc.2012.05.075
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发表时间：
2012-07-15
影响因子：
3.5
通讯作者：
Detty, Michael R.
中科院分区：
文献类型：
--
作者：
Orchard, Alexandra;Schamerhorn, Gregory A.;Calitree, Brandon D.;Sawada, Geri A.;Loo, Tip W.;Bartlett, M. Claire;Clarke, David M.;Detty, Michael R.
已检查了 12 种硫罗丹明衍生物刺激纯化人 P-糖蛋白 (P-gp)-His10 ATP 酶活性的能力，促进钙黄绿素 AM 和长春花碱摄取到多重耐药、P-gp 过表达 MDCKII-MDR1 细胞中的能力，以及它们在多重耐药、单层细胞中的转运速率。 P-gp 过表达 MDCKII-MDR1 细胞。硫罗丹明衍生物具有结构多样性，其结构多样性来自硫罗丹明核心上 2-噻吩基取代基 5 位的酰胺和硫代酰胺官能团（N,N-二乙基和 N-哌啶基），以及 3-氨基取代基与 N,N-二甲基氨基、稠合氮杂萘烷（久洛里啶）和稠合 N-甲基环己胺（半久洛烷基）取代基。久洛啶基和半久洛啶基衍生物是比二甲氨基类似物更有效的P-gp抑制剂。含酰胺衍生物的转运速度比含硫代酰胺衍生物快得多。
Twelve thiorhodamine derivatives have been examined for their ability to stimulate the ATPase activity of purified human P-glycoprotein (P-gp)-His10, to promote uptake of calcein AM and vinblastine into multidrug-resistant, P-gp-overexpressing MDCKII-MDR1 cells, and for their rates of transport in monolayers of multidrug-resistant, P-gp-overexpressing MDCKII-MDR1 cells. The thiorhodamine derivatives have structural diversity from amide and thioamide functionality (N,N-diethyl and N-piperidyl) at the 5-position of a 2-thienyl substituent on the thiorhodamine core and from diversity at the 3-amino substituent with N,N-dimethylamino, fused azadecalin (julolidyl), and fused N-methylcyclohexylamine (half-julolidyl) substituents. The julolidyl and half-julolidyl derivatives were more effective inhibitors of P-gp than the dimethylamino analogues. Amide-containing derivatives were transported much more rapidly than thioamide-containing derivatives.
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影响因子：
7.3
作者：
Gannon MK 2nd;Holt JJ;Bennett SM;Wetzel BR;Loo TW;Bartlett MC;Clarke DM;Sawada GA;Higgins JW;Tombline G;Raub TJ;Detty MR
通讯作者：
Detty MR
影响因子：
3.6
作者：
BEAK, P;BROWN, RA
通讯作者：
BROWN, RA
影响因子：
3.5
作者：
Gibson, SL;Hilf, R;Detty, MR
通讯作者：
Detty, MR
影响因子：
2.8
作者：
Del Valle, DJ;Donnelly, DJ;Detty, MR
通讯作者：
Detty, MR
影响因子：
4.8
作者：
Loo, TW;Bartlett, MC;Clarke, DM
通讯作者：
Clarke, DM