Two new xanthones, characterized as 4-(1,1-dimethylprop-2-enyl)-1,3,5,8-tetrahydroxyxanthone (1) and penangianaxanthone (2), with three known xanthones, cudratricusxanthone H (3), macluraxanthone C (4) and gerontoxanthone C (5), as well as friedelin and stigmasterol were isolated from the leaves of Garcinia penangiana. Their structures were elucidated by analysis of spectroscopic data and comparison of the NMR data with the literature ones. Significant cytotoxicity against DU-145, MCF-7 and NCI-H460 cancer cell lines was demonstrated by compounds 1-5, with IC50 values ranging from 3.5 to 72.8 microM.
Our phytochemical study on the stem bark of Garcinia mangostana has led to the discovery of a new furanoxanthone, mangaxanthone A (1), together with five known analogs. The five known analogs that were isolated are α-mangostin (2), β-mangostin (3), cowagarcinone B (4), and dulcisxanthone F (5). The structural elucidations of these compounds were carried out by interpreting their spectroscopic data, mainly 1D and 2D NMR spectra and MS.
A new tetraoxygenated xanthone, daphnifolin (1,3,5-trihydroxy-4-methoxyxanthone), along with three other xanthones, were isolated from the stem bark extracts of Mesua daphnifolia. Their structures were characterized on the basis of 1D and 2D NMR spectral data.
Two naturally occurring xanthones, ananixanthone (1) and β-mangostin (2), were isolated using column chromatographic method from the n-hexane and methanol extracts of Calophyllum teysmannii, respectively. The major constituent, ananixanthone (1), was subjected to structural modifications via acetylation, methylation and benzylation yielding four new xanthone derivatives, ananixanthone monoacetate (3), ananixanthone diacetate (4), 5-methoxyananixanthone (5) and 5-O-benzylananixanthone (6). Compound 1 together with its four new derivatives were subjected to MTT assay against three cancer cell lines; SNU-1, K562 and LS174T. The results indicated that the parent compound has greater cytotoxicity capabilities against SNU-1 and K562 cell lines with IC50 values of 8.97 ± 0.11 and 2.96 ± 0.06 μg/mL, respectively. Compound 5 on the other hand exhibited better cytotoxicity against LS174T cell line with an IC50 value of 5.76 ± 1.07 μg/mL.
Our continuing studies on secondary metabolites from the stem bark of Calophyllum soulattri has led to the isolation of another new diprenylated xanthone, phylattrin (1), in addition to five other xanthones and two common sterols. The xanthones are soulattrin (2), caloxanthone C (3), macluraxanthone (4), brasixanthone B (5) and trapezifolixanthone (6) while the sterols are stigmasterol (7) and β-sitosterol (8). The structures of these compounds were determined on the basis of spectroscopic analyses such as 1D and 2D-NMR, HRESIMS, IR and UV. Compounds 1-7 exhibited moderate cytotoxic activities against SNU-1, HeLa, Hep G2, NCI-H23, K562, Raji, LS174T, IMR-32 and SK-MEL-28 cells.
A detailed chemical study on the ethyl acetate and methanol extracts of the stem bark of Garcinia mangostana resulted in the successful isolation of one new prenylated xanthone, mangaxanthone B (1), one new benzophenone, mangaphenone (2), and two known xanthones, mangostanin (3) and mangostenol (4). The structures of these compounds were elucidated through analysis of their spectroscopic data obtained using 1D and 2D NMR and MS techniques.
α-Mangostin is an oxygenated heterocyclic xanthone with remarkable pharmacological properties, but poor aqueous solubility and low oral bioavailability hinder its therapeutic application. This study sought to improve the compound's solubility and study the mechanism underlying solubility enhancement. Solid dispersions of α-mangostin were prepared in polyvinylpyrrolidone (PVP) by solvent evaporation method and showed substantial enhancement of α-mangostin's solubility from 0.2 ± 0.2 μg/mL to 2743 ± 11 μg/mL. Fourier transform infrared spectroscopy and differential scanning calorimetry indicated interaction between α-mangostin and PVP. Transmission electron microscopy and dynamic light scattering showed self-assembly of round anionic nanomicelles with particle size in the range 99-127 nm. Powder X-ray diffraction indicated conversion of α-mangostin from crystalline into amorphous state, and scanning electron microscopy showed the presence of highly porous powder. Studies using the fluorescent probe pyrene showed that the critical micellar concentration is about 77.4 ± 4 μg/mL. Cellular uptake of nanomicelles was found to be mediated via endocytosis and indicated intracellular delivery of α-mangostin associated with potent cytotoxicity (median inhibitory concentration of 8.9 ± 0.2 μg/mL). Improved solubility, self-assembly of nanomicelles, and intracellular delivery through endocytosis may enhance the pharmacological properties of α-mangostin, particularly antitumor efficacy.
The air-dried powdered stem bark of Calophyllum nodusum (Guttiferea) collected from Sandakan (Sabah, Malaysia), was extracted sequentially with hexane, chloroform and methanol. The solvents were removed by rotary evaporator to give dark viscous extracts. Detailed and repeated chromatographic separation of the extracts lead to isolation of two new xanthones, identified as nodusuxanthone and trapezifolixanthone A. Other common terpenoids such as betulinic acid, lupeol, stigmasterol and friedelin were also isolated from the extracts and identified. The structures of the compounds were established by detailed spectral analysis and comparison with previously reported data.
A new furanodihydrobenzoxanthone, artomandin (1), together with three other flavonoid derivatives, artoindonesianin C, artonol B, and artochamin A, as well as β-sitosterol were isolated from the stem bark of Artocarpus kemando. The structures of these compounds were determined on the basis of spectral evidence. All of these compounds displayed inhibition effects to a very susceptible degree in cancer cell line tests. Compound 1 also exhibited significant antioxidant capacity in the free radical 1,1-diphenyl-2-picrylhydrazyl tests.
In the authors' continuing search for new natural products, their recent studies on the roots of Calophyllum inophyllum (Guttiferae) have yielded a new prenylated pyranoxanthone, Inophyllin A together with the common triterpenes friedelin and stigmasterol. Structural elucidations of these compounds were achieved through (1)H, (13)C, DEPT, COSY, HSQC and HMBC experiments. The molecular mass was determined using MS techniques. The authors report here the isolation of and structural elucidation for Inophyllin A as well as its toxicity test result. The discovery of this new natural product from the unexploited Malaysian forest will certainly contribute to the search for potential natural larvicides.
The cytotoxic structure-activity relationships among a series of xanthone derivatives from Mesua beccariana, Mesua ferrea and Mesua congestiflora were studied. Eleven xanthone derivatives identified as mesuarianone (1), mesuasinone (2), mesuaferrin A (3), mesuaferrin B (4), mesuaferrin C (5), 6-deoxyjacareubin (6), caloxanthone C (7), macluraxanthone (8), 1,5-dihydroxyxanthone (9), tovopyrifolin C (10) and α-mangostin (11) were isolated from the three Mesua species. The human cancer cell lines tested were Raji, SNU-1, K562, LS-174T, SK-MEL-28, IMR-32, HeLa, Hep G2 and NCI-H23. Mesuaferrin A (3), macluraxanthone (8) and α-mangostin (11) showed strong cytotoxicities as they possess significant inhibitory effects against all the cell lines. The structure-activity relationship (SAR) study revealed that the diprenyl, dipyrano and prenylated pyrano substituent groups of the xanthone derivatives contributed towards the cytotoxicities.
A new pyranoxanthone, venuloxanthone (1), was isolated from the stem bark of Calophyllum venulosum, together with three other xanthones, tovopyrifolin C (2), ananixanthone (3) and caloxanthone I (4), along with two common triterpenes, friedelin (5) and lupeol (6). The structures of these compounds were identified using several spectroscopic analyses which are NMR, GCMS and FTIR experiments.
Many tropical plants have interesting biological activities with potential therapeutic applications. Garcinia mangostana Linn. (GML) belongs to the family of Guttiferae and is named "the queen of fruits". It is cultivated in the tropical rainforest of some Southeast Asian nations like Indonesia, Malaysia, Sri Lanka, Philippines, and Thailand. People in these countries have used the pericarp (peel, rind, hull or ripe) of GML as a traditional medicine for the treatment of abdominal pain, diarrhea, dysentery, infected wound, suppuration, and chronic ulcer. Experimental studies have demonstrated that extracts of GML have antioxidant, antitumoral, antiallergic, anti-inflammatory, antibacterial, and antiviral activities. The pericarp of GML is a source of xanthones and other bioactive substances. Prenylated xanthones isolated from GML have been extensively studied; some members of these compounds possess antioxidant, antitumoral, antiallergic, anti-inflammatory, antibacterial, antifungal and antiviral properties. Xanthones have been isolated from pericarp, whole fruit, heartwood, and leaves. The most studied xanthones are alpha-, beta-, and gamma-mangostins, garcinone E, 8-deoxygartanin, and gartanin. The aim of this review is to summarize findings of beneficial properties of GML's extracts and xanthones isolated from this plant so far.
The α- and γ-mangostins from Garcinia mangostana pericarps (GMP) exhibit antioxidant, anti-bacterial, anti-inflammatory and anti-tumor properties. The extraction yields α- and γ-mangostins are often limited by the presence of the GMP cell walls. Therefore, the extraction and recovery of mangostins from GMP with an Aspergillus niger cellulase-assisted aqueous micellar biphasic system (CA-AMBS) was developed for enhanced yield of mangostins. Effects of the concentration of cellulase, the incubation time and the temperature of the system on the recovery of mangostins were investigated. The optimum condition for the recovery of α- and γ-mangostins was obtained with the addition of 0.5% (w/w) cellulase incubated at 40°C for 2 h. High log partition coefficients of α-mangostins (log Kα 4.79 ± 0.02) and γ-mangostins (log Kγ 4.02 ± 0.02) were achieved. High yields of α-mangostins (73.4%) and γ-mangostins (14.0%) were obtained from the micelle-rich bottom phase with final concentrations of 3.67 mg/mL and 0.70 mg/mL, respectively. The back-extraction of mangostins was performed with the addition of 30% (w/w) of isopropanol and 0.05 M of KCl at pH 9 to the bottom phase of the CA-AMBS. The yields of the α- and γ-mangostins from GMP were considerably enhanced with the CA-AMBS and the direct recovery of mangostins was demonstrated without additional downstream processing steps.
Alzheimer's disease is a neurodegenerative disorder that results in progressive and irreversible central nervous system impairment, which has become one of the severe issues recently. The most successful approach of Alzheimer's treatment is the administration of cholinesterase inhibitors to prevent the hydrolysis of acetylcholine and subsequently improve cholinergic postsynaptic transmission. This review highlights a class of heterocycles, namely xanthone, and its remarkable acetylcholinesterase inhibitory activities. Naturally occurring xanthones, including oxygenated, prenylated, pyrano, and glycosylated xanthones, exhibited promising inhibition effects towards acetylcholinesterase. Interestingly, synthetic xanthone derivatives with complex substituents such as alkyl, pyrrolidine, piperidine, and morpholine have shown greater acetylcholinesterase inhibition activities. The structure-activity relationship of xanthones revealed that the type and position of the substituent(s) attached to the xanthone moiety influenced acetylcholinesterase inhibition activities where hydrophobic moiety will lead to an improved activity by contributing to the π-π interactions, as well as the hydroxy substituent(s) by forming hydrogen-bond interactions. Thus, further studies, including quantitative structure-activity relationship, in vivo and clinical validation studies are crucial for the development of xanthones into novel anti-Alzheimer's disease drugs.
A new series of 3-O-substituted xanthone derivatives were synthesised and evaluated for their anti-cholinergic activities against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The results indicated that the xanthone derivatives possessed good AChE inhibitory activity with eleven of them (5, 8, 11, 17, 19, 21-23, 26-28) exhibited significant effects with the IC50 values ranged 0.88 to 1.28 µM. The AChE enzyme kinetic study of 3-(4-phenylbutoxy)-9H-xanthen-9-one (23) and ethyl 2-((9-oxo-9H-xanthen-3-yl)oxy)acetate (28) showed a mixed inhibition mechanism. Molecular docking study showed that 23 binds to the active site of AChE and interacts via extensive π-π stacking with the indole and phenol side chains of Trp86 and Tyr337, besides the hydrogen bonding with the hydration site and π-π interaction with the phenol side chain of Y72. This study revealed that 3-O-alkoxyl substituted xanthone derivatives are potential lead structures, especially 23 and 28 which can be further developed into potent AChE inhibitors.
One of the most promising plants in biological screening test results of thirteen Artocarpus species was Artocarpus obtusus FM Jarrett and detailed phytochemical investigation of powdered dried bark of the plant has led to the isolation and identification of three xanthones; pyranocycloartobiloxanthone A (1), dihydroartoindonesianin C (2) and pyranocycloartobiloxanthone B (3). These compounds were screened for antioxidant, antimicrobial and tyrosinase inhibitory activities. Pyranocycloartobiloxanthone A (1) exhibited a strong free radical scavenger towards DPPH free radicals with IC50 value of 2 µg/mL with prominent discoloration observed in comparison with standard ascorbic acid, α-tocopherol and quercetin, The compound also exhibited antibacterial activity against methicillin resistant Staphylococcus aureus (ATCC3359) and Bacillus subtilis (clinically isolated) with inhibition zone of 20 and 12 mm, respectively. However the other two xanthones were found to be inactive. For the tyrosinase inhibitory activity, again compound (1) displayed strong activity comparable with the standard kojic acid.
The stem bark extracts of Calophyllum inophyllum furnished one new furanoxanthone, inophinnin (1), in addition to inophyllin A (2), macluraxanthone (3), pyranojacareubin (4), 4-hydroxyxanthone, friedelin, stigmasterol, and betulinic acid. The structures of these compounds were determined by spectroscopic analysis of 1D and 2D NMR spectral data ((1)H, (13)C, DEPT, COSY, HMQC, and HMBC) while EI-MS gave the molecular mass. The new xanthone, inophinnin (1), exhibited some anti-inflammatory activity in nitric oxide assay.
Two new xanthones, pyranocycloartobiloxanthone A (1) and dihydroartoindonesianin C (2), were isolated from the stem bark of Artocarpus obtusus Jarrett by chromatographic separation. Their structures were determined by using spectroscopic methods and comparison with known related compounds. Pyranocycloartobiloxanthone A (1) showed strong free radical scavenging activity by using DPPH assay as well as cytotoxicity towards K562, HL-60, and MCF7 cell lines.
Our current interest in searching for natural anti-cancer lead compounds from plants has led us to the discovery that the stem and roots of Garcinia mangostana can be a source of such compounds. The stem furnished 2,8-dihydroxy-6-methoxy-5-(3-methylbut-2-enyl)-xanthone (1), which is a new xanthone. Meanwhile, the root bark of the plant furnished six xanthones, namely alpha-mangostin (2), beta-mangostin (3), gamma-mangostin (4), garcinone D (5), mangostanol (6), and gartanin (7). The hexane and chloroform extracts of the root bark of G. mangostana as well as the hexane extract of the stem bark were found to be active against the CEM-SS cell line. gamma-Mangostin (4) showed good activity with a very low IC(50) value of 4.7 microg/ml, while alpha-mangostin (2), mangostanol (6), and garcinone D (5) showed significant activities with IC(50) values of 5.5, 9.6, and 3.2 microg/ml, respectively. This is the first report on the cytotoxicity of the extracts of the stem and root bark of G. mangostana and of alpha-mangostin, mangostanol, and garcinone D against the CEM-SS cell line.