Indomethacin-induced spectral responses of naphthalimide-based dyes to serum albumin: effects of substituent and spacer.

Abstract

Four indomethacin-naphthalimide binaries with different proton receptors at 4-position of naphthalimide were designed and synthesized. N,N-Dimethylethylenediamine and N-methyl piperazine were served as proton receptors as well as solubility regulators. Indomethacin, an inhibitor for cyclooxygenase-2 overexpressed on cancer cells, was connected at the imine N through different spacers. The attachment of indomethacin significantly quenched the fluorescence of all compounds with obvious red-shift in the absorption maxima due to the strong photo-induced electron transfer process of the folded-state. Human serum albumin (HSA) triggered about 15-fold fluorescence enhancements of DMN-IMC-5 with 30nm blue-shift. However, it caused much smaller fluorescence increments of other compounds, suggesting that indomethacin, the linker and proton receptor play critical roles in HSA identification. Fluorescence bioimaging results show that indomethacin enables the naphthalimide-based compounds to fluorescent imaging living cells. Molecular docking reveals that the introduction of indomethacin improved the binding affinity of the dyes to HSA.