Cholinesterase Enzymes Inhibitors from the Leaves of Rauvolfia Reflexa and Their Molecular Docking Study

Molecules

Mehran Fadaeinasab²  A. Hamid A. Hadi²  Yalda Kia³  Alireza Basiri¹ 

[1] School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800 Penang, Malaysia; E-Mails:;Department of Chemistry, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia; E-Mail:;School of Chemical Sciences, Universiti Sains Malaysia, 11800 Penang, Malaysia; E-Mail:

关键词: Apocynaceae;    Rauvolfia reflexa;    acetylcholinesterase;    butyrylcholinesterase;    molecular docking;   

DOI  :  10.3390/molecules18043779

来源: mdpi

【 摘 要 】

Plants of the Apocynaceae family have been traditionally used in the treatment of age-related brain disorders. Rauvolfia reflexa, a member of the family, has been used as an antidote for poisons and to treat malaria. The dichloromethane, ethanol and methanol extracts from the leaves of Rauvolfia reflexa showed potential acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities, with IC₅₀ values in the 8.49 to 52.23 g/mL range. Further cholinesterase inhibitory-guided isolation of these extracts afforded four bioactive compounds, namely: (E)-3-(3,4,5-trimethoxyphenyl)acrylic acid (1), (E)-methyl 3-(4-hydroxy-3,5-dimethoxyphenyl) acrylate (2), 17-methoxycarbonyl-14-heptadecaenyl-4-hydroxy-3-methoxycinnamate (3) and 1,2,3,4-tetrahydro-1-oxo-β-carboline (4). The isolated compounds showed moderate cholinesterase inhibitory activity compared to the reference standard, physostigmine. Compounds 1 and 2 showed the highest inhibitory activity against AChE (IC₅₀ = 60.17 µM) and BChE (IC₅₀ = 61.72 µM), respectively. Despite having similar molecular weight, compounds 1 and 2 were structurally different according to their chemical substitution patterns, leading to their different enzyme inhibition selectivity. Compound 2 was more selective against BChE, whereas compound 1 was a selective inhibitor of AChE. Molecular docking revealed that both compounds 1 and 2 were inserted, but not deeply into the active site of the cholinesterase enzymes.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland.