Compounds with Anti-Alzheimer Activity Isolated for the First Time from Melaleuca leucodendron (L.) Leaves

Objective: To discover a drug from natural triterpenes that has no side effects and is effective in treating Alzheimer's disease. We predict that the drug will be put on the market soon and achieve success. Methods: The methanolic extract of M. leucodendron leaves was fractionated and subjected to different chromatographic techniques to isolate two new triterpene glycosides alongside five known compounds kaempferol 3, quercetin 4, quercetin3-O-β-D-glucopyranoside 5, kaempferol3- O-β-D-glucopyranoside 6 and kaempferol3-O-α-L-rhamnoside 7. The structures of compounds 1 and 2 were elucidated by spectroscopic analysis and chemical means. Results: Two new triterpene glycosides, 21-O-α-L-rhamnopyranosyl-olean-12-ene-3-O-[α-Lrhamnopyranosyl (1-4) β-D-galactopyranosyl (1-4) β-D-glucouronopyranoside]1 and 21-O-α-Lrhamnopyranosyl- olean-12-ene-3-O-[α-L-rhamnopyranosyl (1→4) β-D-galactopyra-nosyl (1→4) β-D-galactopyranoside] 2, were isolated for the first time from 70% aqueous methanolic extract (AME) of M. leucodendron leaves. The inhibitory activities of the said compounds toward acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) were then assayed. Both compounds exhibited significant inhibitory activities toward the two enzymes, and evidence indicated that compound 2 was a more effective inhibitor than compound 1. Conclusion: Compounds 1 and 2 have a significant role in inhibiting the enzymes acetylcholinesterase and butyrylcholinesterase.