Heraiz_2025_RSC.Adv_15_49178

Targeting acetylcholinesterase (AChE) and beta-secretase (BACE-1) enzymes is a promising multifaceted approach for treating neurological disorders. In our study, the chemical investigation of Echinocactus grusonii Hildm. (Cactaceae) led to the isolation and identification of seven compounds, including three flavonoids, naringenin 1, kaempferol 2, and isokaempferide 3, one megastigmane glycoside, vomifoliol-9-O-beta-d-glucopyranoside 4, and three alkaloids, N-chloromethyl hordenine 5, N-acetyl hordenine 6, and N-acetyl-N-chloromethyl-N-methyl tyramine 7. Compounds 5 and 7 were identified as previously undescribed halogenated alkaloids. Biological evaluation revealed that all compounds exhibited promising acetylcholinesterase inhibitory activity (IC(50) = 0.076-2.255 microg mL(-1)), as well as significant inhibition of beta-secretase with IC(50) values ranging from 0.066 to 7.189 microg mL(-1). Docking, molecular dynamics, and binding energy calculations suggested that compounds 4 and 5 are promising AChE inhibitors, while compounds 3, 4, and 7 are leading candidates against beta-secretase. Collectively, this study underscores the potential of Echinocactus grusonii as a rich source of bioactive lead compounds for developing novel therapeutics for pharmaceutical applications.