In Vitro and Molecular Docking Evaluation of the Anticholinesterase and Antidiabetic Effects of Compounds from Terminalia macroptera Guill. & Perr. (Combretaceae).

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 α-amylase and α-glucosidase inhibitors are employed as antidiabetic agents. Compounds were isolated from the medicinal plant Terminalia macroptera and evaluated for their AChE, BChE, α-amylase, and α-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-β-D-xylopyranoside ( 2 ), 3,3',4'-tri-O-methyl ellagic acid-4-O-β-D-glucopyranoside ( 3 ), 3,3'-di-O-methyl ellagic acid-4-O-β-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 µg/mL and 50.48 ± 1.10 µg/mL against AChE and BChE, respectively. The compounds exhibited potential inhibition of α-amylase and α-glucosidase, especially the phenolic compounds ( 1 - 5 ). Myricetin-3-O-rhamnoside had the highest α-amylase inhibition with an IC 50 value of 65.17 ± 0.43 µg/mL compared to acarbose with an IC 50 value of 32.25 ± 0.36 µg/mL. Two compounds, 3,3'-di-O-methyl ellagic acid (IC 50 = 74.18 ± 0.29 µg/mL) and myricetin-3-O-rhamnoside (IC 50 = 69.02 ± 0.65 µg/mL), were more active than the standard acarbose (IC 50 = 87.70 ± 0.68 µg/mL) in the α-glucosidase assay. For α-glucosidase and α-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.