Design, Synthesis, and Activity Evaluation of Novel Dual-Target Inhibitors with Antifungal and Immunoregulatory Properties.

Dual-target (CYP51/PD-L1) plays an important role in the process of fungal proliferation and immune suppression. A series of novel quinazoline compounds with dual-target inhibition function was constructed using the skeleton growth method, and their structures were synthesized, characterized, and evaluated. Among them, the perfected compounds ( L11 , L20 , L21 ) were selected for further study, which exhibited remarkable biological activity against different fungal strains (MIC 50 , 0.25-2.0 μg/mL) in vitro . On the one hand, these compounds inhibited CYP51 activity, induced ROS aggregation, and mitochondrial damage; this ultimately caused fungal lysis and death. On the other hand, they also effectively activated the body's immune ability by blocking the interaction between PD-L1 and PD-1, slowed down the inflammatory reaction, and accelerated the recovery process of fungal infections.