Cholinesterase inhibitory activity of isoquinoline alkaloids from three Cryptocarya species (Lauraceae)

Wan Nurul Nazneem Wan Othman, Sook Yee Liew, Kooi Yeong Khaw, Vikneswaran Murugaiyah, Marc Litaudon, Khalijah Awang

Research output: Contribution to journalArticleResearchpeer-review

46 Citations (Scopus)

Abstract

Alzheimer's disease is the most common form of dementia among older adults. Acetylcholinesterase and butyrylcholinesterase are two enzymes involved in the breaking down of the neurotransmitter acetylcholine. Inhibitors for these enzymes have potential to prolong the availability of acetylcholine. Hence, the search for such inhibitors especially from natural products is needed in developing potential drugs for Alzheimer's disease. The present study investigates the cholinesterase inhibitory activity of compounds isolated from three Cryptocarya species towards acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Nine alkaloids were isolated; (+)-nornantenine 1, (−)-desmethylsecoantofine 2, (+)-oridine 3, (+)-laurotetanine 4 from the leaves of Cryptocarya densiflora BI., atherosperminine 5, (+)-N-methylisococlaurine 6, (+)-N-methyllaurotetanine 7 from the bark of Cryptocarya infectoria Miq., 2-methoxyatherosperminine 8 and (+)-reticuline 9 from the bark of Cryptocarya griffithiana Wight. In general, most of the alkaloids showed higher inhibition towards BChE as compared to AChE. The phenanthrene type alkaloid; 2-methoxyatherosperminine 8, exhibited the most potent inhibition against BChE with IC50value of 3.95 μM. Analysis of the Lineweaver–Burk (LB) plot of BChE activity over a range of substrate concentration suggested that 2-methoxyatherosperminine 8 exhibited mixed-mode inhibition with an inhibition constant (Ki) of 6.72 μM. Molecular docking studies revealed that 2-methoxyatherosperminine 8 docked well at the choline binding site and catalytic triad of hBChE (butyrylcholinesterase from Homo sapiens); hydrogen bonding with Tyr 128 and His 438 residues respectively.

Original languageEnglish
Pages (from-to)4464-4469
Number of pages6
JournalBioorganic & Medicinal Chemistry
Volume24
Issue number18
DOIs
Publication statusPublished - 15 Sept 2016
Externally publishedYes

Keywords

  • 2-Methoxyatherosperminine
  • Butyrylcholinesterase
  • Cryptocarya
  • Enzyme kinetic
  • Molecular docking
  • Phenanthrene

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