Antibacterial activity of xanthones from Garcinia mangostana (L.) and their structure-activity relationship studies.

Antibacterial activities of prenylated xanthones from Garcinia mangostana and their synthetic analogues were investigated, and their structure-activity relationships have been studied. γ-Mangostin has shown antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA), methicillin sensitive Staphylococcus aureus (MSSA), vancomycin-resistant Enterococcus (VRE) and vancomycin-sensitive Enterococcus (VSE) strains at MICs 3.13, 6.25, 6.25 and 6.25 µg mL(-1), respectively. In these experiments, gentamicin was used as the positive control. Further, some analogues of γ-mangostin and α-mangostin were synthesised and their activity was tested against MRSA and VRE strains. The analysis of the bioassay results above indicated that, the combination of C-6 and C-3 hydroxyl groups along with the prenyl side chain at C-2 in the 1,3,6,7-tetraoxygenated xanthones from G. mangostana is essential to have a high antibacterial activity.

A new ß-glucuronidase inhibiting butyrolactone from the marine endophytic fungus Aspergillus terreus.

An endophytic fungus Aspergillus terreus, var. boedijnii (Blochwitz) was isolated from red marine alga Laurencia ceylanica, J. Agardh, cultured in large scale and extracted with EtOAc. The above-mentioned extract yielded a new butyrolactone, 3-hydroxy-4-(4-hydroxyphenyl)-5-methoxycarbonyl-5-(4-hydroxy-3-formylbenzyl)-2,5-dihydro-2-furanone (1), along with the previously reported nine compounds, butyrolactone-1 (2), 6-hydroxymellin (3), (3 R, 4 R)-6,7-dimethoxy-4-hydroxymellin (4), (+)-territonin (5), (+)-territonin-A (6), (+)-asterrelenin (7), (+)-terrein (8), oleic acid (9) and glucopyranosyl-ß-sitosterol (10), on column and preparative thin-layer chromatography. Compounds 1-8 were subjected to ß-glucuronidase inhibitory activity test, and 1 showed a remarkable activity, while 2 and 7 showed moderate activity.

New methylethers of cordatolides from Calophyllum cordato-oblongum and their synthesis.

Twigs of Calophyllum cordato-oblongum Thw. have been shown to contain cordatolide A-OMe, cordatolide B-OMe, cordatolide C-OMe, cordatolide A, cordatolide B, oblongulide, cordatooblongic acid, friedelin, canophyllol, and sitosterol. Methylation of cordatolide B and the attempted methylation of cordatolide A under acidic conditions gave cordatolide B-OMe and 11,12-anhydrocordatolide. Cordatolide A-OMe, cordatolide C-OMe and 11,12-anhydrocordatolide are new compounds.

Xanthones from roots of Calophyllum thwaitesii and their bioactivity.

Extracts from three Calophyllum species endemic to Sri Lanka were tested for antifungal and antioxidant activities. Of them, only the root methanol extract of Calophyllum thwaitesii showed activity, and the active extract on activity guided fractionation yielded four antifungal active and three inactive xanthones. Antifungal active xanthones were identified as 1,6-dihydroxy-5-methoxyxanthone, 1-hydroxy-5,6-dimethoxyxanthone, 1-hydroxy-5-methoxyxanthone and 1-methoxy-5-hydroxyxanthone, using spectroscopic methods and comparison with literature data. Inactive compounds were identified as 1-hydroxy-7-methoxyxanthone, 1,5-dihydroxy-6-methoxyxanthone and 1,7-dihydroxy xanthone. This is the first report of above xanthones except the latter from C. thwaitesii. Further, five of the above xanthones along with thwaitesixanthone and calothwaitesixanthone, which have been previously reported from the root bark of the same species, showed free radical scavenging properties when tested with DPPH. Further, this is the first report of methylated xanthones from C. thwaitesii. Previous work on stem bark, root bark and the stem of the same species yielded only nonmethylated xanthones, indicating the absence of methylating enzymes in the plant. However, this new finding suggests the presence of methylating enzymes in the root stem of C. thwaitesii.

Antibacterial activity of alpha-mangostin against vancomycin resistant Enterococci (VRE) and synergism with antibiotics.

alpha-Mangostin, isolated from the stem bark of Garcinia mangostana L., was found to be active against vancomycin resistant Enterococci (VRE) and methicillin resistant Staphylococcus aureus (MRSA), with MIC values of 6.25 and 6.25 to 12.5 microg/ml, respectively. Our studies showed synergism between alpha-mangostin and gentamicin (GM) against VRE, and alpha-mangostin and vancomycin hydrochloride (VCM) against MRSA. Further studies showed partial synergism between alpha-mangostin and commercially available antibiotics such as ampicillin and minocycline. These findings suggested that alpha-mangostin alone or in combination with GM against VRE and in combination with VCM against MRSA might be useful in controlling VRE and MRSA infections.

A geranylated biphenyl derivative from Garcinia malvgostana.

Extracts of root bark, stem bark and the latex collected from the green fruits of Garcinia mangostana gave alpha-mangostin, beta-mangostin, gamma-mangostin, garcinone-E, methoxy-beta-mangostin and a new geranylated biphenyl derivative 3-hydroxy-4-geranyl-5-methoxybiphenyl. The latex of G. mangostana consists of more than 75% of xanthones which have strong antibacterial (anti-MRSA and -VRE), anti-inflammatory, antifungal and a number of other biological activities. Hence the presence of the above highly bioactive compounds in large quantities should be the causative factor for G. mangostana's medicinal value in indigenous medicine.

Determination of saponins and alkaloids in Caulophyllum thalictroides (blue cohosh) by high-performance liquid chromatography and evaporative light scattering detection.

The roots of Caulophyllum thalictroides, traditionally used for the treatment of menstrual difficulties and as an aid in childbirth, contain saponins, which are considered to be responsible for the uterine stimulant effects, together with teratogenic alkaloids. An HPLC method has been developed which permits the determination of the triterpene saponins in the plant and also the separation of four alkaloids. The best results were obtained with a C-12 stationary phase using ammonium acetate buffer (pH 8.0) and acetonitrile as mobile phase. Owing to their low UV absorbance, the saponins were detected by evaporative light scattering, whereas the alkaloids were monitored by UV at 310 nm. The identities of the compounds were confirmed in an LC-MS experiment. Different plant samples and commercial products have been analysed using the described method, and remarkable qualitative and quantitative variations were revealed. Comparing the daily uptake of total saponins, a difference of greater than 100-fold was observed within the various products; the alkaloid content on the other hand was more uniform.

Antibacterial activity of calozeyloxanthone isolated from Calophyllum species against vancomycin-resistant Enterococci (VRE) and synergism with antibiotics.

Calozeyloxanthone ( 1) was re-isolated from the root bark of Calophyllum moonii, an endemic species of Sri Lanka, and found to be active against vancomycin-resistant Enterococci (VRE) and vancomycin-sensitive Enterococci (VSE) with MIC values of 6.25 microg/ml and 12.5 microg/ml, respectively. Further, a marked synergism between 1 and vancomycin hydrochloride (VCM) against VRE was also observed. These findings suggest that 1 in combination with VCM against VRE may be useful in controlling VRE infections.

Inhibition of HIV-1 reverse transcriptase and HIV-1 replication by Calophyllum coumarins and xanthones.

As part of our continuing study on the Calophyllum species, a number of coumarins, xanthones and chromene acids from different Calophyllum species of Sri Lanka were tested for inhibitory activity against the HIV-1 and its virally-encoded reverse transcriptase (RT). These compounds were found to be inactive in both the HIV-1 RT and whole virus systems. In contrast, cordatolide A and B demonstrated IC(50) values of 19.3 and 11.7 microM, respectively, against HIV-1 replication in a novel green fluorescent protein (GFP)-based reporter cell assay (HOG.R5).