Nat Prod Sci.  2018 Jun;24(2):88-92. 10.20307/nps.2018.24.2.88.

Garcinexanthone G, a Selective Butyrylcholinesterase Inhibitor from the Stem Bark of Garcinia atroviridis

• Khaw KY
• Murugaiyah V
• Khairuddean M
• Tan WN

• KMID: 2416067
• DOI: http://doi.org/10.20307/nps.2018.24.2.88

Abstract

The present study was undertaken to investigate the isolated compounds from the stem bark of Garcinia atroviridis as potential cholinesterase inhibitors and the ligand-enzyme interactions of selected bioactive compounds in silico. The in vitro cholinesterase results showed that quercetin (3) was the most active AChE inhibitor (12.65 ± 1.57 µg/ml) while garcinexanthone G (6) was the most active BChE inhibitor (18.86 ± 2.41 µg/ml). It is noteworthy to note that compound 6 was a selective inhibitor with the selectivity index of 11.82. Molecular insight from docking interaction further substantiate that orientation of compound 6 in the catalytic site which enhanced its binding affinity as compared to other xanthones. The nature of protein-ligand interactions of compound 6 is mainly hydrogen bonding, and the hydroxyl group of compound 6 at C-10 is vital in BChE inhibition activity. Therefore, compound 6 is a notable lead for further drug design and development of BChE selective inhibitor.

Keyword

Garcinia atroviridis; Garcinexanthone G; Butyrylcholinesterase; Molecular docking

MeSH Terms

Butyrylcholinesterase*
Catalytic Domain
Cholinesterase Inhibitors
Cholinesterases
Computer Simulation
Drug Design
Garcinia*
Hydrogen Bonding
In Vitro Techniques
Quercetin
Xanthones
Butyrylcholinesterase
Cholinesterase Inhibitors
Cholinesterases
Quercetin
Xanthones

Figure

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  Fig. 1. The structures of compounds 1 – 6 from the stem bark of G. atroviridis.

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  Fig. 2. Binding interactions of compounds 4 – 6 and galanthamine with the amino acids of butyrylcholinesterase. A-D represents compounds 4 – 6 and galanthamine, respectively.

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