Feunaing_2024_Molecules_29_

Alzheimer's disease (AD) and diabetes are non-communicable diseases with global impacts. Inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are suitable therapies for AD, while alpha-amylase and alpha-glucosidase inhibitors are employed as antidiabetic agents. Compounds were isolated from the medicinal plant Terminalia macroptera and evaluated for their AChE, BChE, alpha-amylase, and alpha-glucosidase inhibitions. From (1)H and (13)C NMR data, the compounds were identified as 3,3'-di-O-methyl ellagic acid (1), 3,3',4'-tri-O-methyl ellagic acid-4-O-beta-D-xylopyranoside (2), 3,3',4'-tri-O-methyl ellagic acid-4-O-beta-D-glucopyranoside (3), 3,3'-di-O-methyl ellagic acid-4-O-beta-D-glucopyranoside (4), myricetin-3-O-rhamnoside (5), shikimic acid (6), arjungenin (7), terminolic acid (8), 24-deoxysericoside (9), arjunglucoside I (10), and chebuloside II (11). The derivatives of ellagic acid (1-4) showed moderate to good inhibition of cholinesterases, with the most potent being 3,3'-di-O-methyl ellagic acid, with IC(50) values of 46.77 +/- 0.90 microg/mL and 50.48 +/- 1.10 microg/mL against AChE and BChE, respectively. The compounds exhibited potential inhibition of alpha-amylase and alpha-glucosidase, especially the phenolic compounds (1-5). Myricetin-3-O-rhamnoside had the highest alpha-amylase inhibition with an IC(50) value of 65.17 +/- 0.43 microg/mL compared to acarbose with an IC(50) value of 32.25 +/- 0.36 microg/mL. Two compounds, 3,3'-di-O-methyl ellagic acid (IC(50) = 74.18 +/- 0.29 microg/mL) and myricetin-3-O-rhamnoside (IC(50) = 69.02 +/- 0.65 microg/mL), were more active than the standard acarbose (IC(50) = 87.70 +/- 0.68 microg/mL) in the alpha-glucosidase assay. For alpha-glucosidase and alpha-amylase, the molecular docking results for 1-11 reveal that these compounds may fit well into the binding sites of the target enzymes, establishing stable complexes with negative binding energies in the range of -4.03 to -10.20 kcalmol(-1). Though not all the compounds showed binding affinities with cholinesterases, some had negative binding energies, indicating that the inhibition was thermodynamically favorable.