Isolation, identification and in silico evaluation of novel cholinesterase inhibitors from Terminalia triptera Stapf
學年 114
學期 2
出版（發表）日期 2026-03-27
作品名稱 Isolation, identification and in silico evaluation of novel cholinesterase inhibitors from Terminalia triptera Stapf
作品名稱（其他語言）
著者 Phan TQ, Huang HT, Wang SL, Nguyen DS, Doan MD, Pham THT, Phan TKT, Truong BP, Nguyen VB
單位
出版者
著錄名稱、卷期、頁數 Molecules, 31(7), 1113
摘要 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.
關鍵字 Terminalia triptera; cholinesterase inhibitors; Alzheimer’s disease; DFT; molecular docking; molecular dynamics
語言 en
ISSN
期刊性質 國外
收錄於 SCI
產學合作
通訊作者 Wang, San-Lang
審稿制度 1
國別 CHE
公開徵稿
出版型式 ,電子版