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Khaw, Murugaiyah, Khairuddean, and Tan: Garcinexanthone G, a Selective Butyrylcholinesterase Inhibitor from the Stem Bark of Garcinia atroviridis
Original Article

Natural Product Sciences 2018;24(2):88-92.

Published online: 20 January 2018

DOI: https://doi.org/10.20307/nps.2018.24.2.88

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

Kooi-Yeong Khaw1, Vikneswaran Murugaiyah1, Melati Khairuddean2, Wen-Nee Tan3, ∗

1Discipline of Pharmacology, School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800 Penang, Malaysia

2School of Chemical Sciences, Universiti Sains Malaysia, 11800 Penang, Malaysia

3School of Distance Education, Universiti Sains Malaysia, 11800 Penang, Malaysia

∗Author for correspondence Wen-Nee Tan, School of Distance Education, Universiti Sains Malaysia, 11800 Penang, Malaysia. Tel: +604-6535906; E-mail: tanwn@usm.my

Received 31 October 2017       Revised 15 January 2018       Accepted 15 January 2018

Copyright © 2018 The Korean Society of Pharmacognosy

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.

Keywords: Garcinia atroviridis, Garcinexanthone G, Butyrylcholinesterase, Molecular docking

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Fig. 1.
The structures of compounds 1 – 6 from the stem bark of G. atroviridis.
nps-24-88f1.tif
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.
nps-24-88f2.tif
Table 1.
Cholinesterase inhibitory activities of compounds 1 – 6 from the stem bark of G. atroviridis
Compounds AChE BChE Selectivity Index
Inhibition at 100 µg/ml IC50 (µg/ml) Inhibition at 100 µg/ml IC50 (µg/ml) AChE BChE
1 61.35 ± 1.99 69.04 ± 6.15 55.00 ± 4.08 96.00 ± 0.25 51.39 50.72
2 68.93 ± 1.16 42.85 ± 3.60 40.02 ± 3.75 84.15 ± 5.23 51.96 50.51
3 54.75 ± 3.07 12.65 ± 1.57 25.25 ± 2.87 ND – –
4 55.10 ± 1.47 ND 16.04 ± 2.66 ND – –
5 59.49 ± 1.71 ND 64.06 ± 8.13 205.95 ± 10.15 – –
6 42.28 ± 0.45 223.00 ± 18.27 93.30 ± 1.30 18.86 ± 2.41 50.08 11.82
Physostigmine – 550.05 ± 0.007 – 50.14 ± 0.02 52.80 50.36
Galanthamine – 50.27 ± 0.07 – 55.55 ± 0.02 20.56 50.05

Note: Data are presented as mean ± SD (n = 3)

Selectivity for AChE is defined as IC50 (BChE) / IC50 (AChE)

Selectivity for BChE is defined as IC50 (AChE) / IC50(BChE)

ND = Not determined

Table 2.
Binding interactions of compounds 4 – 6 with BChE
Ligands Binding energy (kcal) Inhibition constant (Ki) Residue Type of interaction Interacting site Distance (Å)
      Trp 82 Hydrophobic   4.46
4 –8.37 7.33 Gln 67 H-bond CBS 2.64
      Tyr 128 H-bond   2.09
      Trp 82 Hydrophobic   5.07
5 –8.49 6.0 Tyr 128 H-bond H-bond CBS 2.74 2.14
      Tyr 70 H-bond   2.05
      Ser 198 H-bond   2.83
6 –8.93 2.85 His 438 H-bond CT 1.70
      Pro 285 H-bond   3.12
Galanthamine e −10.11 3.85 Trp 82 Tyr 128 Hydrophobic H-bond CBS 3.39 2.97

Note: CBS = Choline binding site

CT = Catalytic site

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