Prenylated xanthones from mangosteen as promising cholinesterase inhibitors and their molecular docking studies

被引:71
作者
Khaw, K. Y. [1 ]
Choi, S. B. [2 ]
Tan, S. C. [3 ]
Wahab, H. A. [4 ]
Chan, K. L. [5 ]
Murugaiyah, V. [1 ]
机构
[1] Univ Sains Malaysia, Sch Pharmaceut Sci, Discipline Pharmacol, George Town 11800, Malaysia
[2] Univ Sains Malaysia, Bioproc Div, Sch Ind Technol, George Town 11800, Malaysia
[3] Univ Sains Malaysia, Inst Res Mol Med INFORMM, George Town 11800, Malaysia
[4] Univ Sains Malaysia, Sch Pharmaceut Sci, Pharmaceut Design & Simulat PhDS Lab, George Town 11800, Malaysia
[5] Univ Sains Malaysia, Sch Pharmaceut Sci, Discipline Pharmaceut Chem, George Town 11800, Malaysia
关键词
Acetylcholinesterase; Butyrylcholinesterase; alpha-Mangostin; gamma-Mangostin; Garcinone C; Molecular docking; ACETYLCHOLINESTERASE; DISEASE; FRUIT;
D O I
10.1016/j.phymed.2014.06.017
中图分类号
Q94 [植物学];
学科分类号
071001 ;
摘要
Garcinia mangostana is a well-known tropical plant found mostly in South East Asia. The present study investigated acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities of G. mangostana extract and its chemical constituents using Ellman's colorimetric method. Cholinesterase inhibitory-guided approach led to identification of six bioactive prenylated xanthones showing moderate to potent cholinesterases inhibition with IC50 values of lower than 20.5 mu M. The most potent inhibitor of AChE was garcinone C while gamma-mangostin was the most potent inhibitor of BChE with IC50 values of 1.24 and 1.78 mu M, respectively. Among the xanthones, mangostanol, 3-isomangostin, garcinone C and alpha-mangostin are AChE selective inhibitors, 8-deoxygartanin is a BChE selective inhibitor while gamma-mangostin is a dual inhibitor. Preliminary structure-activity relationship suggests the importance of the C-8 prenyl and C-7 hydroxy groups for good AChE and BChE inhibitory activities. The enzyme kinetic studies indicate that both alpha-mangostin and garcinone C are mixed-mode inhibitors, while gamma-mangostin is a non-competitive inhibitor of AChE. In contrast, both gamma-mangostin and garcinone Care uncompetitive inhibitors, while alpha-mangostin is a mixed-mode inhibitor of BChE. Molecular docking studies revealed that alpha-mangostin, gamma-mangostin and garcinone C interacts differently with the five important regions of AChE and BChE. The nature of protein-ligand interactions is mainly hydrophobic and hydrogen bonding. These bioactive prenylated xanthones are worthy for further investigations. (C) 2014 Elsevier GmbH. All rights reserved.
引用
收藏
页码:1303 / 1309
页数:7
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