Isolation, identification and in silico evaluation of novel cholinesterase inhibitors from Terminalia triptera Stapf

doi:10.3390/molecules31071113

機構典藏 > College of Sciences > Graduate Institute & Department of Chemistry > Journal Article > Item 987654321/129168

Please use this identifier to cite or link to this item: https://tkuir.lib.tku.edu.tw/dspace/handle/987654321/129168

Title:	Isolation, identification and in silico evaluation of novel cholinesterase inhibitors from Terminalia triptera Stapf
Authors:	TQ, Phan;HT, Huang;SL, Wang;DS, Nguyen;MD, Doan;THT, Pham;TKT, Phan;BP, Truong;VB, Nguyen
Keywords:	Terminalia triptera;cholinesterase inhibitors;Alzheimer’s disease;DFT;molecular docking;molecular dynamics
Date:	2026/03/27
Issue Date:	2026-04-07 12:05:29 (UTC+8)
Publisher:	MDPI
Abstract:	Alzheimer’s disease (AD) remains a significant global health challenge, highlighting the need for novel dual inhibitors targeting acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). This study investigated the trunk bark of Terminalia triptera Stapf. as a potential source of bioactive secondary metabolites for AD management. Bioassay-guided isolation led to the identification of two flavan-3-ol derivatives, epicatechin-(4β→8)-ent-catechin (1) and (−)-catechin (2), reported here for the first time from this species. In vitro assays demonstrated that the dimeric compound 1 exhibited stronger dual inhibitory activity against AChE and BChE, with IC50 values of 4.41 × 10−4 and 4.75 × 10−4 mol/L, respectively, surpassing the reference compound berberine chloride. Molecular docking analysis revealed that compound 1 formed extensive interactions within both catalytic and peripheral anionic sites of the enzymes. Density Functional Theory (DFT) calculations indicated high kinetic stability, reflected by large HOMO–LUMO energy gaps (6.66–6.97 eV), while global reactivity descriptors suggested lower electrophilicity (ω = 2.19–2.34 eV), supporting a potentially favorable safety profile. Furthermore, 100 ns molecular dynamics simulations confirmed stable ligand–protein complexes stabilized by hydrogen-bond networks and deep binding within catalytic pockets. Overall, these findings highlight T. triptera and its dimeric proanthocyanidins as promising multi-target candidates for anti-Alzheimer drug development.
Relation:	Molecules 31(7), p.1113
DOI:	10.3390/molecules31071113
Appears in Collections:	[Graduate Institute & Department of Chemistry] Journal Article

Files in This Item:

File	Description	Size	Format
index.html		0Kb	HTML	31	View/Open

Loading...