The development of novel AIE-active staurosporine-based fluorescent probes with theranostic potential

Abstract

The research on the photophysical properties and structure–activity relationships of staurosporine derivatives is highly meaningful to develop staurosporine as a new type of anticancer therapeutic. In this work, three staurosporine derivatives (Y1, Y2 and Y3) with aggregation-induced emission (AIE) characteristics and theranostic potential were designed and synthesized by using cyano electron-withdrawing groups to modify the natural staurosporine. These new staurosporine derivatives exhibited AIE properties and solvatochromism. The photoluminescence quantum yields of Y1, Y2, and Y3 are enhanced by factors of 4.3, 5.9, and 7.1 in the aggregated state, respectively. These fluorescent probes also showed protein kinase C (PKC) inhibitory activity and anti-cancer activity for NCI-N87 and MCF-7 cells. The docking calculations revealed that the probes retained antitumor activity by preserving key interactions between the staurosporine core and the protein kinase C (PKC). Cellular imaging demonstrated bright fluorescence emission within tumor cells. This work provides a design strategy for integrating fluorescence performance and pharmacological activity, offering a promising approach for cancer diagnosis and therapy.