Daturaolone from Datura metel L. Inhibits acetylcholinesterase and monoamine oxidase B

Daturaolone is an amyrin-type triterpenoid isolated from Datura metel L. which was evaluated in the current study as a multitarget inhibitor of enzymes implicated in neurodegeneration, namely acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), and monoamine oxidase B (MAO-B). While no significant inhibition was detected towards BuChE, daturaolone inhibited AChE (IC50 = 45.06 ± 1.80 µM), even if with lower potency if compared to the positive control donepezil (IC50 = 0.047 ± 0.001 µM). Concerning MAO-B, daturaolone displayed an IC50 value of 28.04 ± 1.68 µM, higher of that of positive control safinamide (IC50 = 0.027 ± 0.001 µM). Molecular docking was used to study the binding to the catalytic sites of the macromolecular targets, while ligand-based studies predicted low-affinity interactions with protein phosphatases, androgen receptor, and β-secretase 1, along with limited drug-likeness.