A Dihydrochalcone from Syzygium samarangense with Anticholinesterase Activity
Evangeline C. Amor1*, Irene M. Villaseñor1, Sarfraz Ahmad Nawaz2,
M. Sabir Hussain2 and M. Iqbal Choudhary2
1Institute of Chemistry, College of Science, University of the Philippines,
Diliman 1101 Quezon City, Philippines
2International Center for Chemical Sciences at HEJ Research Institute of Chemistry, University of Karachi, Karachi 75270, Pakistan
corresponding author: This email address is being protected from spambots. You need JavaScript enabled to view it.
ABSTRACT
Cholinesterase inhibitors are known to be useful in the treatment of neurodegenerative disorders such as Alzheimer’s disease, senile dementia, and ataxia. These had also been found to improve long term memory processes by enhancing cholinergic activity. Herbs rich in flavonoids were shown to have therapeutic effects on neurodegenerative diseases. Flavonoids isolated from Syzygium samarangense, locally known in the Philippines as “makopa”, identified from spectral data as 7-hydroxy-5-methoxy-6,8-dimethylflavanone (1), 2’-hydroxy-4’,6’-dimethoxy-3’-methylchalcone (2), 2’,4’-dihydroxy-6’-methoxy-3’,5’-dimethylchalcone (3), 2’,4’-dihydroxy-6’-methoxy-3’-methylchalcone (4), and 2’,4’-dihydroxy-6’-methoxy-3’-methyldihydrochalcone (5), were tested for anticholinesterase activity against two cholinesterases, acetylcholinesterase (3.1.1.7), and butyrylcholinesterase (3.1.1.8). Compounds 2 and 3 were hydrogenated to yield 2’-hydroxy-4’,6’-dimethoxymethoxy-3’-methyldihyrdochalcone (6) and 2’,4’-dihydroxy-6’-methoxy-3’,5’-dimethyl-dihydrochalcone (7), respectively. Compound 7 exhibited 98.5% inhibitory activity against acetylcholinesterase at 0.25 mM concentration. When tested against butyrylcholinesterase, it exhibited 68.0% inhibitory activity at 0.20 mM concentration and its IC50 was determined to be 127 µM. The IC50 of physostigmine, the positive control, was 0.041 µM and 0.857 µM against acetylcholinesterase and butyrylcholinesterase, respectively. The rest of the compounds did not exhibit significant inhibition of the cholinesterases. This is the first report of anticholinesterase activity of compound 7, a dihydrochalcone.
INTRODUCTION
Enzyme assays are used to discover bioactive compounds that interfere with a specific enzyme-mediated biological reaction (Devlin 1997). Anticholinesterases are being utilized in the treatment of neurodegenerative diseases such as Alzheimers's disease (McGleenon et al. 1999; Rosenthal 2002) senile dementia . . . .
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