AIM OF THE STUDY: The present study was intended to evaluate anti-cholinesterase potential of 177 Malaysian plant extracts from 148 species known to have related ethnomedicinal uses such as anti-inflammatory, anti-oxidant, anti-diabetic, epilepsy, headache, memory enhancement and anti-aging.
MATERIALS AND METHODS: Anti-cholinesterase screening against both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes was performed on the basis of in-vitro colorimetric 96-well microplate-based assay method. Potent active plant extracts were subjected to liquid-liquid extraction and acid-base fractionation for further analysis.
RESULTS: Fifty-seven plant extracts exhibited potent anti-cholinesterase activities (50-100% inhibition) at 200 μg/ml. Majority of the active plants originated from Fabaceae family. Coccoloba uvifera (L.) L. stem extract manifested the lowest IC50 of 3.78 μg/ml for AChE and 5.94 μg/ml for BChE. A few native species including Tetracera indica (Christm. & Panz.) Merr., Cyrtostachys renda Blume and Ixora javanica (Blume) DC. showed cholinesterase inhibition despite limited local medical applications. Further anti-AChE evaluation (50 μg/ml) of 18 potent plant extracts harbored active polar components in butanol and water fractions, except Senna pendula (Willd.) H.S.Irwin & Barneby (leaves and stems), Acacia auriculiformis Benth. (leaves), Artocarpus altilis (Parkinson ex F.A.Zorn) Fosberg (leaves), and Macaranga tanarius (L.) Mull.Arg. (leaves) that showed inhibitory activity in less polar fractions. The acidic extraction of these four plant species improved their inhibition level against AChE.
CONCLUSION: This study rendered a preliminary overview of anti-cholinesterase activity from diverse Malaysian botanical families in which provided the medical relevance toward these native plant species, especially ones with limited ethnobotanical record or practice.
METHODS: The synthesized compounds were evaluated for their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory potential by modified Ellman's method. The molecular interactions between the most active compound and the enzyme were analyzed by molecular docking.
RESULTS: Among them, 3j displayed higher inhibitory activities than reference drug, galanthamine, with IC50 values of 2.05 and 5.77 µM, for AChE and BChE, respectively. Interestingly, all the compounds except 3b displayed higher BChE inhibitions than galanthamine with IC50 values ranging from 5.77 to 18.52 µM. Molecular docking of compound 3j inside the TcAChE and hBChE completely coincided with the inhibitory activities observed. The compound forms strong hydrogen bonding at the peripheral anionic site of AChE whereas on BChE, it had hydrophobic and mild polar interactions.
CONCLUSION: An efficient and eco-friendly synthetic methodology has been developed to synthesize Schiff bases in a very short reaction time and excellent yields in ionic solvent, whereby the compounds from series 3 showed promising cholinesterase inhibitory activity.