Natural Corynanthe-Type Cholinesterase Inhibitors from Malaysian Uncaria attenuata Korth. Isolation, Characterization, In Vitro and In Silico Studies

Nelson Jeng Yeou Chear, Tan Ai Fein Ching-Ga, Kooi Yeong Khaw, Francisco León, Wen Nee Tan, Siti R. Yusof, Christopher R. McCurdy, Vikneswaran Murugaiyah, Surash Ramanathan

Research output: Contribution to journalArticleResearchpeer-review

Abstract

The Uncaria genus is notable for its therapeutic potential in treating age-related dementia, such as Alzheimer’s disease. A phytochemical study of the leaves of Malaysian Uncaria attenuata Korth., afforded an undescribed natural corynanthe-type oxindole alkaloid, isovillocarine D (1) together with two known indole alkaloids, villocarine A (2) and geissoschizine methyl ether (3), and their structural identification was performed with extensive mono- and bidimensional NMR and MS spectroscopic methods. The isolated alkaloids were evaluated for their acetylcholinesterase (AChE)- and butyrylcholinesterase (BChE)-inhibitory activity. The results indicated that compound (2) was the most potent inhibitor against both AChE and BChE, with IC50 values of 14.45 and 13.95 µM, respectively, whereas compounds (1) and (3) were selective BChE inhibitors with IC50 values of 35.28 and 17.65 µM, respectively. In addition, molecular docking studies revealed that compound (2) interacts with the five main regions of AChE via both hydrogen and hydrophobic bonding. In contrast to AChE, the interactions of (2) with the enzymatic site of BChE are established only through hydrophobic bonding. The current finding suggests that U. attenuata could be a good source of bioactive alkaloids for treating age-related dementia.

Original languageEnglish
Article number390
Number of pages12
JournalMetabolites
Volume13
Issue number3
DOIs
Publication statusPublished - Mar 2023

Keywords

  • acetylcholinesterase
  • butyrylcholinesterase
  • indole
  • molecular docking
  • oxindole
  • Uncaria attenuata

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