This article throws light upon the top ten activities of xanthones. The activities are: 1. Biological Activities 2. Antimalarial Activity 3. Antitumor Activity 4. Antimicrobial Activity 5. Antioxidant Activity 6. Anti-Inflammatory Activity 7. The Antifungal Activity 8. Alpha-Glucosidase Inhibitory Activity 9. Anti-Tubercular Activity 10. Trypanocidal Activity.
Activity # 1. Biological Activities :
Many naturally occurring xanthones, their xanthone-O-glucosides, xanthone-C-glucosides and synthetic poly-oxygenated xanthones have been found to possess a number of significant biological activities.
Many plants of medicinal importance have shown the presence of xanthonic constituents to which their therapeutic properties may be attributed. The plants containing xanthones are used mainly as laxative, as diuretic, for liver troubles, in mental disorders- insanity, epilepsy, and nervous debility and also in tuberculosis.
Activity # 2. Antimalarial Activity:
The antimalarial activity of 22 xanthones against chloroquine resistant strains of Plasmodium falciparum was evaluated. Natural caloxanthone-C, De-methyl-calaba-xanthone, Calothwaitesixanthone, Calozeyloxanthone, dombakinaxanthone, macluraxanthone, and 6-deoxy-gamma-mangos- tin were isolated from Calophyllum caledonicum.
The relationship between antimalarial activity and molecular structure of xanthones has also been explored. The most potent xanthones, and (IC50 = c.a. 1.0 mg/mL) are 1, 3, 7 tri-oxygenated and prenylated on the 2 and 8 positions.
Five xanthones from the bark of Carcinia cowa, namely 7-O-methylgarcinone E, cowanin, cowanol, cowaxanthone, and beta-mangostin, were found to possess in vitro antimalarial activity against Plasmodium falciparum with IC50 values ranging from 1.50 to 3.00 µg/ml.
A series of 3, 6-bis-ω-di-ethyl-amino-alkoxyxanthones with side chains ranging from 2 to 8 carbon atoms were prepared and evaluated. Measurement of heme affinity for each of the derivatives revealed a strong correlation (R2 = 0.97) between affinity and antimalarial potency.
The two most active compounds in the series contained 5- and 6-carbon side chains and exhibited low Nano molar 50% inhibitory concentration (IC50) values against strains of chloroquine-susceptible and multidrug-resistant Plasmodium falciparum in vitro.
Both of these xanthones exhibit stronger heme affinity (8.26 x 10s and 9.02 x 10s M_1, respectively) than either chloroquine or quinine under similar conditions and appear to complex heme in a unique manner.
Xanthones with a hydroxyl group in the peri-position exhibited decreased antimalarial activity, possibly due to intermolecular hydrogen bonding with the carbonyl and consequent reduced affinity for heme. Paired hydroxyls attached to the lower half of the xanthone greatly enhanced drug potency.
The synthesis and antimalarial properties of twelve new chlorinated 9H-xanthones, carrying a [2-(di-ethyl-amino) ethyl] amino group in position 1 are reported. All compounds were found to be active towards the chloroquine-susceptible and chloroquine-resistant strains 3D7 and Dd2, of Plasmodium falciparum.
The phytochemical study of the methanol extract of the stem bark of Allanblackia monticola STANER L.C. resulted in the isolation of a new prenylated xanthenedione, designated as allanxanthone C, together with the five known xanthones, garciniafuran, tovophyllin A, rubraxanthone, norcowanin and mangostin and one saponin, stigmasterol- 3-O- b-D-glucopyranoside.
The structure of the new compound was established by spectroscopic analysis as 1,2-dihydro-3,6,8-trihy-droxy-1,1,7-tri (3-methylbut-2-enyl) xanthen-2,9- dione (3- hydroxyapetalinone C). The methanol extract and pure compounds were tested on two strains of Plasmodium falciparum, F32 (chloroquine sensitive) and FcM29 (chloroquine resistant). The IC50 values obtained ranged from 0.6 to 8.9 mg/ml.
Activity # 3. Antitumor Activity:
The effects of six xanthones from the pericarps of mangosteen, Carcinia mangostana, on the cell growth inhibition of human leukemia cell line HL60 were examined. All xanthones displayed growth inhibitory effects. Among them, alpha-mangostin showed complete inhibition at 10 mi- croM through the induction of apoptosis.
This finding that crude alphamangostin has potent chemo preventive effects in our short-term colon carcinogenesis bioassay system suggests that longer exposure might result in suppression of tumor development.
Xanthones bearing different functionalities, namely-hydroxyxanthone, 3-hydroxyxanthone, 1,4-dihydroxyxanthone, 2,6-dihydroxyxanthone, 1,2-diacetoxyxanthone, 2,6-diacetoxyxanthone,3- methoxyxanthone,1,3,7-trimethoxyxanthone and 1,5-dihydroxy-6-methoxyxanthone were synthesized and examined for their effect on nicotinamide adenine dinucleotide phosphate (NADPH)- catalysed liver microsomal lipid peroxidation and on tumour necrosis factor-α (TNF-α) induced expression of intercellular adhesion molecule-1 (ICAM-1) on endothelial cells, with a view to establish structure-activity relationship.
Hydroxy- and acetoxyxanthones showed potent inhibitory effects on NADPH-catalyzed lipid peroxidation and TNF-α induced expression of ICAM-1 on endothelial cells.
Results have shown that one of the xanthone derivatives which could be identified as garcinone E has potent cytotoxic effect on all HCC cell lines as well as on the other gastric and lung cancer cell lines included in the screen.
The chemo preventive action of xanthone derivatives bellidifolin, gentiacaulein, norswertianin and swerchirin on DNA damage photosensitized by riboflavin was demonstrated using [32P]-5′-end-labeled DNA fragments obtained from genes relevant to human cancer, gentiacaulein and norswertianin effectively inhibited the formation of piperidine-labile products at consecutive G residues by photoexcited riboflavin. Xanthone derivatives have been shown to be potent inhibitors of tumour growth.
Oxygenated Xanthones and [3- (dialkylamino)-2-hydroxypropoxy]s have been prepared and tested for in-vitro inhibition of human PLC/PRF/5, KB and 212 cells. Structure-activity analysis indicated epoxidation of the hydroxyxanthone increased cytotoxicity against tumour cells but ring-opening of the epoxide group with dialkylamine did not enhance the anti-tumour activity.
Further evaluation of three of the most active compounds 2, 6-, 3, 6-, and 3, 5-di (2, 3- epoxypropoxy) xanthone in DNA, RNA and protein synthesis of tumour cells showed potent inhibitory activity.
The new benzopyranoxanthone derivatives only displayed marginal anti-proliferative activity when tested against L1210 and KB-3-1 cell lines. The only compounds found significantly active against LI 210 cell line, 16 and 20, belong to the benzo [a] pyrano [3,2-h] xanthen-7-one series, which possess a pyran ring fused angularly onto the xanthone basic core.
The effects of the prenylated xanthonic derivatives on then vitro growth of four human tumour cell lines: MCF-7 (breast), NCI- H460 (non-small cell lung), SF-268 (central nervous system) and UACC-62 (melanoma) were evaluated and found to be selective and highly potent against the MCF-7 cell line.
Two new xanthone derivatives were isolated from Polygala vulgaris and were tested for in vitro cytotoxic activity using two cell lines, LoVo and its strain, which express resistance to common antitumor agents.
Two new xanthones 1,5,6-trihydroxy-6′,6′- dimethyl-2H-pyrano(2′,3′:3,4)-2-(3-methylbut-2- enyl) xanthone and 1,6,7-trihydroxy-6′,6′-dime- thyl-2H-pyrano(2′,3′:3,2)-4-(3-methylbut-2- enyl)xanthone, have been isolated from the stem bark of Carcinia lancilimba (Guttiferae), together with six known xanthones.
Their structures were identified on the basis of extensive spectral evidence including detailed 2D NMR and HR-MS data. Two new compounds showed moderate inhibitory effect on human breast cancer MDA-MB- 435S cell line.
Activity # 4. Antimicrobial Activity:
Calozeloxanthone, a xanthone which has been isolated from Calophyllum moonii and Calophyllum lankensis, showed the highest activity against methicillin-resistant S. aureus (MRSA) strains at a concentration of 8.3 µg/ml.
A number of flavone and xanthone derivatives bearing some characteristic features of Fluoro quinolones such as the fluorine atom and an ortho piperazine ring are described. The new compounds have been tested for possible cytotoxic and antimicrobial activities. Cytotoxicity of both groups of compounds is rather poor, while the antibacterial activity is restricted to xanthones.
Activity # 5. Antioxidant Activity:
Two xanthones, alpha- and gamma-mangostins, were isolated from the fruit bull of Carcinia mangostana, and both significantly inhibited nitric oxide (NO) and PGE2 production from lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. The IC50 values for the inhibition of NO production by alpha- and gamma-mangostins were 12.4 and 10.1muM, respectively.
Chemical investigation of the n-butanol extract from the methanol extract of the root bark of Artocarpus nobilis furnished four new prenylated flavonoids together with Artonin E 2′-methylether, isoarton- in E 2′-methyl ether, dihydroisoartonin E 2′-meth- ylether, Artonin V 2′-methyl ether artobiloxanthone, artonin E and cycloartobiloxanthone.
All these compounds showed strong radical scavenging properties towards DPPH radical. Substances with anti-oxidative properties were obtained from an ether extract of Swertia japonica Makino.
Six active components of the extract were isolated and identified as methylbellidifolin, methylswertianin, swertianin, bellidifolin, norswertianin and desmethylbellidifolin. These six xanthone derivatives were shown to possess different antioxidant activities by chemiluminescent assay.
The anti-oxidative activities of bellidifolin, norswertianin and desmethylbellidifolin were higher than those of butylated hydroxytoluene (BHT) and a-tocopherol. On autooxidation of methyl linoleate, bellidifolin had activity similar to that of BHT.
Activity # 6. Anti-Inflammatory Activity:
1, 5-dihydroxy-3, 8-dimethoxy xanthone of Swertia chirata showed significant anti-inflammatory action in acute, sub-acute and chronic experimental models in rats. Gamma-Mangostin had a potent inhibitory activity of prostaglandin E2 (PGE2) release induced by A23187, a Ca2+ ionophore with the IC50 value of about 5 microM.
In enzyme assay in vitro, gamma-mangostin inhibited the activities of both constitutive COX-I and inducible COX-II in a concentration- dependent manner, with the IC50 values of about 0. 8 and 2 microM, respectively.
2-Hydroxyacetyl-7-acetylxanthone, a new xanthone derivative, was synthesized in four steps starting from xanthene, by two synthetic approaches. The new compound displayed antianaphylactic activity in the PCA test and in the anaphylaxis shock test in rats. It also displayed analgesic activity in the writhing test in mice, and anti-inflammatory activity in the carrageenan edema test in rats.
Activity # 7. The Antifungal Activity:
The antifungal activity of several xanthones isolated from the fruit hulls of Carcinia mangostana and some derivatives of mangostin against three phytopathogenic fungi, Fusarium oxysporum vasinfectum, Alternaria tenuis, and Dreschlera oryzae, has been evaluated.
The natural xanthones showed good inhibitory activity against the three fungi. Substitution in the A and C rings has been shown to modify the bioactivities of the compounds.
Activity # 8. Alpha-Glucosidase Inhibitory Activity:
The results indicated that these xanthone derivatives were capable of inhibiting in vitro alpha-glucosidase with moderate to good activities.
Among them, polyhydroxylxanthones exhibited the highest activities and thus may be exploitable as a lead compound for the development of potent alpha – glucosidase inhibitors. A series of novel xanthone derivatives with extended π- systems, that is, benzoxanthones and their structurally perturbed analogs have been designed and synthesized as α-glucosidase inhibitors.
Their inhibitory activities toward yeast α-glucosidase were evaluated with the aim to enrich the structure – activity relationship. The results indicated that benzoxanthones were capable of inhibiting in vitro yeast α-glucosidase.
Activity # 9. Anti-Tubercular Activity:
Alpha- and beta-mangostins and garcinone B exhibited strong inhibitory effect against Mycobacterium tuberculosis with the minimum inhibitory concentration (MIC) value of 6.25 µg/ml.
Activity # 10. Trypanocidal Activity:
The constituents of the stem bark of Carcinia sub-elliptica (Guttiferae) were investigated based on its trypanocidal activity against epimastigotes of Trypanosoma cruzi, the etiologic agent for Cha-gas’ disease. As the active components, nine xanthones were isolated including two new ones, 4- hydroxybrasilixanthone B and 1,3,5,6- tetrahydroxy-4,7,8-tri (3-methyl-2-butenyl) xanthone.