3.1 Discovery of a small molecule DACA against MPP+-induced neuronal cells
The potential protective effects of rosemary diterpenes, namely carnosic acid (CA), carnosol (CS), and rosmarinol (RO), were investigated in SH-SY5Y cells. Our results demonstrated that CS significantly enhanced the viability of MPP+-induced SH-SY5Y cells, surpassing CA and RO (Fig. 2B). Consequently, we synthesized a carnosol derivative named DACA through a simple structural modification of carnosol (Fig. 2C-D). Notably, DACA exhibited superior anti- MPP+ activity compared to carnosol alone without any apparent cytotoxicity towards cells (Fig. 2E). To further validate the neuroprotective effect of DACA, we used MPP+ to stimulate primary neurons to evaluate its impact. Our findings revealed that DACA effectively inhibited MPP+-induced injury in primary neurons while exhibiting no influence on primary neuron survival when administered alone (Fig. 2E). Collectively, these findings highlight DACA as a valuable small molecule capable of safeguarding against MPP+- induced neuronal cell injury.