Anticholinesterase Activity of Budmunchiamine Alkaloids Revealed by Comparative Chemical Profiling of Two <i>Albizia</i> spp., Molecular Docking and Dynamic Studies
Mai E. Hussein,
Osama G. Mohamed,
Ahlam M. El-Fishawy,
Hesham I. El-Askary,
Ahmed A. Hamed,
Marwa M. Abdel-Aziz,
Radwan Alnajjar,
Amany Belal,
Ahmed M. Naglah,
Abdulrahman A. Almehizia,
Ahmed A. Al-Karmalawy,
Ashootosh Tripathi,
Amira S. El Senousy
Affiliations
Mai E. Hussein
Pharmacognosy Department, Faculty of Pharmacy, Cairo University, Kasr el Aini St., Cairo 11562, Egypt
Osama G. Mohamed
Pharmacognosy Department, Faculty of Pharmacy, Cairo University, Kasr el Aini St., Cairo 11562, Egypt
Ahlam M. El-Fishawy
Pharmacognosy Department, Faculty of Pharmacy, Cairo University, Kasr el Aini St., Cairo 11562, Egypt
Hesham I. El-Askary
Pharmacognosy Department, Faculty of Pharmacy, Cairo University, Kasr el Aini St., Cairo 11562, Egypt
Ahmed A. Hamed
Microbial Chemistry Department, National Research Centre, 33 El-Buhouth Street, Dokki, Giza 12622, Egypt
Marwa M. Abdel-Aziz
Regional Center for Mycology and Biotechnology (RCMB), Al-Azhar University, Cairo 11651, Egypt
Radwan Alnajjar
Department of Chemistry, Faculty of Science, University of Benghazi, Benghazi 16063, Libya
Drug Exploration and Development Chair (DEDC), Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
Abdulrahman A. Almehizia
Drug Exploration and Development Chair (DEDC), Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
Ahmed A. Al-Karmalawy
Pharmaceutical Chemistry Department, Faculty of Pharmacy, Ahram Canadian University, 6th of October City, Giza 12566, Egypt
Ashootosh Tripathi
Natural Products Discovery Core, Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA
Amira S. El Senousy
Pharmacognosy Department, Faculty of Pharmacy, Cairo University, Kasr el Aini St., Cairo 11562, Egypt
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.
