Affiliations 

  • 1 Department of Chemistry, Faculty of Science, Universiti Malaya, Kuala Lumpur, Malaysia
  • 2 School of Pharmacy, Monash University Malaysia, Subang Jaya, Selangor, Malaysia
  • 3 Department of Pharmacy, Faculty of Mathematics and Natural Sciences, Tadulako University, Palu, Indonesia
  • 4 Department of Pharmaceutical Science, Faculty of Pharmacy, Airlangga University, Surabaya, Indonesia
  • 5 Centre for Natural Products Research and Drug Discovery (CENAR), Universiti Malaya, Kuala Lumpur, Malaysia
Nat Prod Res, 2024 Aug 21.
PMID: 39165195 DOI: 10.1080/14786419.2024.2394096

Abstract

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 µg/mL. Compound 2, is the most potent inhibitor, exhibiting an IC50 value of 22.08 µM, followed by 1 and 3 (IC50 23.96 and 30.32 µM, 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 μM. 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 β-protein in a transgenic Caenorhabditis elegans (CL4176) model.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.