Indole alkaloids from <i>Ochreinauclea maingayi</i> (Rubiaceae) as butyrylcholinesterase inhibitors and their paralysis effect in transgenic <i>Caenorhabditis elegans</i>

This study investigated the butyrylcholinesterase (BChE) inhibitory activity of harmane (<b>1</b>), naucledine (<b>2</b>), and dihydrodeglycocadambine (<b>3</b>) isolated from fractions F7 and F9 of <i>Ochreinauclea maingayi</i>. Both fractions demonstrated significant inhibition, exceeding 80%, against BChE at 100 µg/mL. Compound <b>2</b>, is the most potent inhibitor, exhibiting an IC₅₀ value of 22.08 µM, followed by <b>1</b> and <b>3</b> (IC₅₀ 23.96 and 30.32 µM, respectively). Docking studies revealed that <b>1</b> and <b>2</b> effectively bind to BChE, with binding energies of -51.24 and -57.17 kcal/mol, respectively. Kinetic analysis of <b>2</b> indicated mixed-mode inhibition of BChE, with a <i>Ki</i> of 6.08 μM. In the paralysis assay, <b>1</b> 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 <b>2</b> with 70.00 ± 1.7% (2.59% reduction) compared with negative standard (DMSO 0.1%) on human amyloid <i>β</i>-protein in a transgenic <i>Caenorhabditis elegans</i> (CL4176) model.