A bi-functional fluorescent probe for visualized and rapid natural drug screening via GSTs activity monitoring

•A bi-functional fluorescent probe RP as the GSTs substrate and drug screening tool.•A new method applicable to visualized and rapid natural drug screening.•Natural compound C7 screened as GSTs inhibitor. Glutathione S-transferase (GSTs), as an important target for drug screening, is closely associated with physiological and pathological process regulation. Hence, effective monitoring of GSTs activity is benificial for GSTs-induced diseases diagnosis and therapeutic drugs discovery. Resorufin-typed probes with high sensitivity, excellent selectivity, and low cytotoxicity have become a powerful tool for target monitoring. In this study, a bi-functional fluorescent probe, resorufin-typed probe (RP) with resorufin as a fluorophore was designed as the GSTs substrate and drug screening tool. GSTs can trigger significant fluorescence signal enhancement of RP by catalyzing the combination of glutathione (GSH) and its recognition site in RP. Meaningfully, the change of fluorescence signal positively correlated with GSTs activity can be used to monitor the regulatory effect of natural drugs on GSTs. Based on the axis relation of “drug-GSTs activity-fluorescence signal”, this powerful probe was successfully employed for visual and rapid screening GSTs-targeted natural compounds in vitro by monitoring the change of GSTs activity. Natural compound 1, 2 and 7 (C1, C2 and C7) were screened as the GSTs inhibitors, and C7 was helpful for enhancing the sensitivity of cisplatin in cancer cells. Overall, the designed natural drug screening strategy based on bi-functional fluorescence probe demonstrated its hopeful application to drug rapid discovery.