Structure–activity studies of uptake and phototoxicity with heavy-chalcogen analogues of tetramethylrosamine in vitro in chemosensitive and multidrug-resistant cells

Abstract

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 × 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.