8-Deoxygartanin

Phytomedicine. 2014 Sep 25;21(11):1303-9.

Prenylated xanthones from mangosteen as promising cholinesterase inhibitors and their molecular docking studies.[Pubmed: 25172794]

Garcinia mangostana is a well-known tropical plant found mostly in South East Asia.
METHODS AND RESULTS:
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 μM. The most potent inhibitor of AChE was garcinone C while γ-mangostin was the most potent inhibitor of BChE with IC50 values of 1.24 and 1.78 μM, respectively. Among the xanthones, mangostanol, 3-isomangostin, garcinone C and α-mangostin are AChE selective inhibitors, 8-Deoxygartanin is a BChE selective inhibitor while γ-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 α-mangostin and garcinone C are mixed-mode inhibitors, while γ-mangostin is a non-competitive inhibitor of AChE. In contrast, both γ-mangostin and garcinone C are uncompetitive inhibitors, while α-mangostin is a mixed-mode inhibitor of BChE.
CONCLUSIONS:
Molecular docking studies revealed that α-mangostin, γ-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.

Neurochem Res. 2016 Jul;41(7):1806-17.

Natural Xanthones from Garcinia mangostana with Multifunctional Activities for the Therapy of Alzheimer's Disease.[Pubmed: 27038926 ]

Natural xanthones have diversity pharmacological activities.
METHODS AND RESULTS:
Here, a series of xanthones isolated from the pericarps of Garcinia mangostana Linn, named α-Mangostin, 8-Deoxygartanin, Gartanin, Garciniafuran, Garcinone C, Garcinone D, and γ-Mangostin were investigated. Biological screening performed in vitro and in Escherichia coli cells indicated that most of the xanthones exhibited significant inhibition of self-induced β-amyloid (Aβ) aggregation and also β-site amyloid precursor protein-cleaving enzyme 1, acted as potential antioxidants and biometal chelators. Among these compounds, α-Mangostin, Gartanin, Garcinone C and γ-Mangostin showed better antioxidant properties to scavenge Diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl (DPPH) free radical than Trolox, and potent neuroprotective effects against glutamate-induced HT22 cell death partly by up-regulating HO-1 protein level and then scavenging reactive oxygen species. Moreover, Gartanin, Garcinone C and γ-Mangostin could be able to penetrate the blood-brain barrier (BBB) in vitro.
CONCLUSIONS:
These findings suggest that the natural xanthones have multifunctional activities against Alzheimer's disease (AD) and could be promising compounds for the therapy of AD.

Chem Pharm Bull (Tokyo). 2008 Mar;56(3):374-7.

Endodesmiadiol, a friedelane triterpenoid, and other antiplasmodial compounds from Endodesmia calophylloides.[Pubmed: 18310952]

METHODS AND RESULTS:
From the ethyl acetate extract of the stem bark of Endodesmia calophylloides (Guttiferae), a novel friedelane triterpenoid named endodesmiadiol (1), as well as the known compounds friedelin (2), canophyllol (3), canophyllal (4), cerin (5), morelloflavone (6), volkensiflavone (7), 8-Deoxygartanin (8), 3 beta-acetoxyoleanolic acid (9) and 1,8-dihydroxy-3-isoprenyloxy-6-methylxanthone (10) have been isolated. The structures of these compounds were established by spectroscopic analysis, and the relative configuration of endodesmiadiol (1) was confirmed by X-ray diffraction. The antiplasmodial activity of the isolated compounds was evaluated against the W2 strain of Plasmodium falciparum which is resistant to chloroquine and other antimalarial drugs.
CONCLUSIONS:
All the compounds were found to be active with IC50 values ranging from 7.2 to 23.6 microM. The IC50 of endodesmiadiol was found to be 11.8 microM.

Biomed Res Int. 2013;2013:715603.

Altered mRNA expression related to the apoptotic effect of three xanthones on human melanoma SK-MEL-28 cell line.[Pubmed: 24175297 ]

We previously demonstrated that α-mangostin, γ-mangostin, and 8-Deoxygartanin have significant cytotoxic effects on human melanoma SK-MEL-28 cell line. The current study revealed the underlying mechanisms.
METHODS AND RESULTS:
α-Mangostin (7.5  μg/mL) activated caspase activity, with a 3-fold and 4-fold increased caspase 8 and 9 activity, respectively. The molecular mechanisms were investigated by qRT-PCR for mRNA related to cell cycle arrest in G1 phase (p21(WAF1) and cyclin D1), apoptosis (cytochrome C, Bcl-2, and Bax), and survival pathways (Akt1, NFκB, and IκBα). α-Mangostin significantly upregulated mRNA expression of cytochrome C and p21(WAF1) and downregulated that of cyclin D1, Akt1, and NFκB. γ-Mangostin significantly downregulated mRNA expression of Akt1 and NFκB and upregulated p21(WAF1) and IκBα. 8-Deoxygartanin significantly upregulated the mRNA expression of p21(WAF1) and downregulated that of cyclin D1 and NFκB. The three xanthones significantly inhibited the mRNA expression of the BRAF V600E mutation. Moreover, α-mangostin and γ-mangostin significantly downregulated Akt phosphorylation at Ser473.
CONCLUSIONS:
In conclusion, the three xanthones induced an inhibitory effect on SK-MEL-28 cells by modulating the molecular targets involved in the apoptotic pathways.

Food Chem Toxicol. 2011 Sep;49(9):2385-91.

Cytotoxic effect of xanthones from pericarp of the tropical fruit mangosteen (Garcinia mangostana Linn.) on human melanoma cells.[Pubmed: 21723363]

Mangosteen (Garcinia mangostana Linn.) is a tropical tree from South East Asia and its fruit pericarp is a well-known traditional medicine.
METHODS AND RESULTS:
In this study, the cytotoxic effect of three xanthone compounds (α-mangostin, γ-mangostin, and 8-Deoxygartanin) from mangosteen pericarp was investigated using the human melanoma SK-MEL-28 cell line. Significant dose-dependent reduction in % cell viability was induced. γ-Mangostin and 8-Deoxygartanine at 5 μg/ml increased the cell cycle arrest in G(1) phase (90% and 92%) compared with untreated cells (78%). All compounds induced apoptosis, of the highest being α-mangostin at 7.5 μg/ml that induced 59.6% early apoptosis, compared to 1.7% in untreated cells. The apoptotic effect of α-mangostin was via caspase activation and disruption of mitochondrial membrane pathways as evidenced by 25-fold increased caspase-3 activity and 9-fold decreased mitochondrial membrane potential when compared to untreated cells.
CONCLUSIONS:
In conclusion, these xanthones, especially α-mangostin, are potential candidates as anti-melanoma agents.

J Nat Prod. 2009 Nov;72(11):2028-31.

Cytotoxic xanthone constituents of the stem bark of Garcinia mangostana (mangosteen).[Pubmed: 19839614 ]

METHODS AND RESULTS:
Bioassay-guided fractionation of a chloroform-soluble extract of Garcinia mangostana stem bark, using the HT-29 human colon cancer cell line and an enzyme-based ELISA NF-kappaB assay, led to the isolation of a new xanthone, 11-hydroxy-3-O-methyl-1-isomangostin (1). The structure of 1 was elucidated by spectroscopic data analysis. In addition, 10 other known compounds, 11-hydroxy-1-isomangostin (2), 11alpha-mangostanin (3), 3-isomangostin (4), alpha-mangostin (5), beta-mangostin (6), garcinone D (7), 9-hydroxycalabaxanthone (8), 8-Deoxygartanin (9), gartanin (10), and cratoxyxanthone (11), were isolated.
CONCLUSIONS:
Compounds 4-8 exhibited cytotoxicity against the HT-29 cell line with ED50 values of 4.9, 1.7, 1.7, 2.3, and 9.1 microM, respectively. In an ELISA NF-kappaB assay, compounds 5-7, 9, and 10 inhibited p65 activation with IC50 values of 15.9, 12.1, 3.2, 11.3, and 19.0 microM, respectively, and 6 showed p50 inhibitory activity with an IC50 value of 7.5 microM. Alpha-mangostin (5) was further tested in an in vivo hollow fiber assay, using HT-29, LNCaP, and MCF-7 cells, but it was found to be inactive at the highest dose tested (20 mg/kg).