Abstract
AIM: Alzheimer's disease poses a serious global health challenge, and there is an urgent need for novel therapeutic agents, as existing drugs have limited efficacy and notable adverse effects. Chromenones, known for their diverse biological activities, have emerged as promising drug candidates for AD treatment due to their capacity to target multiple enzymes. In this study, investigated the chromenone derivative 8-methoxypsoralen (8-MOP) as a potential multi-target inhibitor of key AD targets, highlighting the importance of the scaffold in target-based drug design. MATERIAL AND METHODS: 8-MOP, a phytochemical extracted and isolated from parsley leaves, was utilized to synthesize new derivatives, which were then screened against enzymes involved in AD progression (BACE1, AChE, BuChE) and targets involved in oxidative pathways (DPPH, NO). In support of the in vitro activity, in silico ADMET predictions and docking experiments were performed. RESULTS AND CONCLUSIONS: Among the synthesized compounds, 3d and 3e demonstrated significant inhibitory effects against the chosen targets, exhibiting IC(50) values between 5.8 ± 0.13 μM and 13 ± 0.12 μM. Furthermore, the docking experiments showed important binding interactions of these compounds with BACE1, AChE, and BuChE. The study demonstrates the potential of 8-MOP derivatives for targeting AD drug targets.