Anticholinesterase Activity of Budmunchiamine Alkaloids Revealed by Comparative Chemical Profiling of Two Albizia spp., Molecular Docking and Dynamic Studies

Abstract

Alzheimer’s disease remains a global health challenge and an unmet need requiring innovative approaches to discover new drugs. The current study aimed to investigate the inhibitory activity of Albizia lucidior and Albizia procera leaves against acetylcholinesterase enzyme in vitro and explore their chemical compositions. Metabolic profiling of the bioactive plant, A. lucidior, via UHPLC/MS/MS-based Molecular Networking highlighted the richness of its ethanolic extract with budmunchiamine alkaloids, fourteen budmunchiamine alkaloids as well as four new putative ones were tentatively identified for the first time in A. lucidior. Pursuing these alkaloids in the fractions of A. lucidior extract via molecular networking revealed that alkaloids were mainly concentrated in the ethyl acetate fraction. In agreement, the alkaloid-rich fraction showed the most promising anticholinesterase activity (IC50 5.26 µg/mL) versus the ethanolic extract and ethyl acetate fraction of A. lucidior (IC50 24.89 and 6.90 µg/mL, respectively), compared to donepezil (IC50 3.90 µg/mL). Furthermore, deep in silico studies of tentatively identified alkaloids of A. lucidior were performed. Notably, normethyl budmunchiamine K revealed superior stability and receptor binding affinity compared to the two used references: donepezil and the co-crystallized inhibitor (MF2 700). This was concluded based on molecular docking, molecular dynamics simulations and molecular mechanics generalized born/solvent accessibility (MM–GBSA) calculations.

The In Vitro Evaluation of Cholinesterase Inhibition and The Antioxidant Effect of Cupressus arizonica Greene, Cupressus lusitanica Mill. and Pinus canariensis C.Sm. Aerial Parts

“…So, both anticholinesterase and antioxidant capabilities are crucial for a medication suitable for treating AD. 18 In order to discover a new therapeutic agent for AD from available natural sources with fewer side effects than other synthetic ones, 19 the © 2024 the authors. This work is licensed under the Creative Commons Attribution 4.0 International License current work aims to provide evidence of the preventive and therapeutic properties of three coniferous plants.…”

Cholinesterase Inhibitors from an Endophytic Fungus Aspergillus niveus Fv-er401: Metabolomics, Isolation and Molecular Docking

“…ChEIs improve cognition and behavior in some patients with AD, including tacrine, rivastigmine, donepezil and galantamine. However, they have several side effects, such as bradycardia, nausea, stomach pain, anorexia and diarrhea [ 12 ].…”

“…On the other hand, molecular docking studies represent the most essential and available types of computational chemistry nowadays. It helps to investigate the possible mechanism of action and target interactions for a particular drug candidate and compare it to a common reference [ 12 , 32 , 33 ].…”

Identification of Antimicrobial Metabolites from the Egyptian Soil-Derived Amycolatopsis keratiniphila Revealed by Untargeted Metabolomics and Molecular Docking

“…Molecular networking using the Global Natural Products Social Molecular Networking (GNPS) web-based platform has proven its applicability in analyzing large sets of MS data. In addition, many tools available on GNPS can conduct an automated search for spectral matches aided by public spectral libraries [ 14 , 15 ]. In addition, the chemical environment within a metabolomics experiment can be assessed using the molecular networking tool provided by (GNPS) [ 16 ].…”