Gibson Scott L, Holt Jason J, Ye Mao, Donnelly David J, Ohulchanskyy Tymish Y, You Youngjae, Detty Michael R
Department of Biochemistry and Biophysics, University of Rochester Medical Center, NY 14641, USA.
Bioorg Med Chem. 2005 Dec 1;13(23):6394-403. doi: 10.1016/j.bmc.2005.06.056. Epub 2005 Aug 9.
Several thio and seleno analogues of tetramethylrosamine (TMR) were prepared. Thio derivatives of TMR have absorption maxima near 570 nm, while seleno derivatives of TMR have absorption maxima near 580 nm. The 3- or 4-N,N-dimethylaminophenyl substituent in the 9-position greatly increases internal conversion, which lowers quantum yields for fluorescence and the generation of singlet oxygen. Thio and seleno analogues of TMR are effective photosensitizers against chemosensitive AUXB1 cells in vitro and against multidrug-resistant CR1R12 cells in vitro, which have been treated with verapamil. The CR1R12 cells accumulated significantly lower concentrations of the photosensitizers relative to the AUXB1 cells presumably due to the expression of P-glycoprotein (Pgp) in the CR1R12 cells. Following treatment with 5 x 10(-5) M verapamil, the uptake in CR1R12 cells of several fluorescent thio analogues of TMR is comparable to that observed for the chemosensitive AUXB1 cells.
制备了几种四甲基玫瑰胺（TMR）的硫代和硒代类似物。TMR的硫代衍生物在570 nm附近有吸收最大值，而TMR的硒代衍生物在580 nm附近有吸收最大值。9位上的3-或4-N，N-二甲基氨基苯基取代基大大增加了内转换，这降低了荧光量子产率和单线态氧的产生。TMR的硫代和硒代类似物是体外针对化学敏感的AUXB1细胞以及体外针对用维拉帕米处理过的多药耐药CR1R12细胞的有效光敏剂。相对于AUXB1细胞，CR1R12细胞积累的光敏剂浓度显著更低，这可能是由于CR1R12细胞中P-糖蛋白（Pgp）的表达。在用5×10⁻⁵ M维拉帕米处理后，几种TMR的荧光硫代类似物在CR1R12细胞中的摄取与在化学敏感的AUXB1细胞中观察到的摄取相当。
