Osman_2024_Nat.Prod.Res__1

This study investigated the butyrylcholinesterase (BChE) inhibitory activity of harmane (1), naucledine (2), and dihydrodeglycocadambine (3) isolated from fractions F7 and F9 of Ochreinauclea maingayi. Both fractions demonstrated significant inhibition, exceeding 80%, against BChE at 100 microg/mL. Compound 2, is the most potent inhibitor, exhibiting an IC(50) value of 22.08 microM, followed by 1 and 3 (IC(50) 23.96 and 30.32 microM, respectively). Docking studies revealed that 1 and 2 effectively bind to BChE, with binding energies of -51.24 and -57.17 kcal/mol, respectively. Kinetic analysis of 2 indicated mixed-mode inhibition of BChE, with a Ki of 6.08 microM. In the paralysis assay, 1 showed a weak delay in paralysis and reduced the paralysis ratio from 72.59 +/- 4.7% to 60.00 +/- 7.0% (12.59% reduction) followed by 2 with 70.00 +/- 1.7% (2.59% reduction) compared with negative standard (DMSO 0.1%) on human amyloid beta-protein in a transgenic Caenorhabditis elegans (CL4176) model.