Naturally Occurring Calanolides: Occurrence, Biosynthesis, and Pharmacological Properties Including Therapeutic Potential.

Calanolides are tetracyclic 4-substituted dipyranocoumarins. Calanolide A, isolated from the leaves and twigs of Calophyllum lanigerum var. austrocoriaceum (Whitmore) P. F. Stevens, is the first member of this group of compounds with anti-HIV-1 activity mediated by reverse transcriptase inhibition. Calanolides are classified pharmacologically as non-nucleoside reverse transcriptase inhibitors (NNRTI). There are at least 15 naturally occurring calanolides distributed mainly within the genus Calophyllum, but some of them are also present in the genus Clausena. Besides significant anti-HIV properties, which have been exploited towards potential development of new NNRTIs for anti-HIV therapy, calanolides have also been found to possess anticancer, antimicrobial and antiparasitic potential. This review article provides a comprehensive update on all aspects of naturally occurring calanolides, including their chemistry, natural occurrence, biosynthesis, pharmacological and toxicological aspects including mechanism of action and structure activity relationships, pharmacokinetics, therapeutic potentials and available patents

Anti-MRSA Activity of Oxysporone and Xylitol from the Endophytic Fungus Pestalotia sp. Growing on the Sundarbans Mangrove Plant Heritiera fomes

Heritiera fomes Buch.-Ham., a mangrove plant from the Sundarbans, has adapted to a unique habitat, muddy saline water, anaerobic soil, brackish tidal activities and high microbial competition. Endophytic fungal association protects this plant from adverse environmental conditions. This plant is used in Bangladeshi folk medicine, but it has not been extensively studied phytochemically, and there is hardly any report on investigation on endophytic fungi growing on this plant. In this study, endophytic fungi were isolated from the surface sterilized cladodes and leaves of H. fomes. The antimicrobial activities were evaluated against two Gram-positive and two Gram-negative bacteria and the fungal strain, Candida albicans. Extracts of Pestalotia sp. showed activities against all test bacterial strains, except that the EtOAc extract was inactive against E. coli. The structures of the purified compounds, oxysporone and xylitol, were elucidated by spectroscopic means. The anti-MRSA potential of the isolated compounds were determined against various MRSA strains, i.e., ATCC 25923, SA-1199B, RN4220, XU212, EMRSA-15 and EMRSA-16, with MIC values ranging from 32-128 g/mL. This paper, for the first time, reports on the anti-MRSA property of oxysporone and xylitol, isolation of the endophyte Pestalotia sp. from H. fomes, and isolation of xylitol from a Pestalotia sp

Cytotoxicity of Libyan Juniperus phoenicea against Human Cancer Cell Lines A549, EJ138, Hepg2 and MCF7

Background: The current study was undertaken to assess the cytotoxicity of the leaves of Libyan Juniperus phoenicea (Cupressaceae) against human cancer cell lines. Methods: The cytotoxicity of the n-hexane, dichloromethane (DCM) and methanol (MeOH) extracts of the leaves of J. phoenicea (JP), obtained from sequential Soxhlet extractions, was assessed against four human cancer cell lines: EJ138 (human bladder carcinoma), HepG2 (human liver hepatocellular carcinoma), A549 (human lung carcinoma) and MCF7 (human breast adenocarcinoma) using the MTT assay. Results: The cell line A549 was the most sensitive to the JP extracts, with the highest level of cytotoxicity with the IC50 values of 16, 13 and 100 µg/mL for the DCM, n-hexane and MeOH extracts, respectively. However, generally the most potent cytotoxic extract across the other cells tested was the n-hexane extract, followed by the DCM extract, whilst the MeOH extracts showed little or no cytotoxicity. The percentage of viability of cells decreased as the concentration of test compounds increased. The cytotoxicity of various chromatographic fractions from the extracts was also studied against the A459 cells. For the n-hexane fractions, the IC50 values were 160, 62, 90, 30, 9.5 and 40 µg/mL for fractions 1 to 5 and 7, respectively. Fractions 4 and 5 showed the greatest effect. DCM fractions 2, 3 and 4 had the IC50 values of 60, 92 and 19 µg/mL, respectively, and DCM fractions 5 to 8 were non-cytotoxic. Fractions 1 and 2 of the MeOH extract were non-cytotoxic, whereas cytotoxicity was observed for fractions 3 and 4 with IC50 values of 50 and 85 µg/mL, respectively. Conclusion: The outcome of the present study suggested that the JP leaves possess cytotoxic activities. The high level of cytotoxicity of the n-hexane and DCM extracts suggested that lipophilicity might affect the cytotoxicity of JP, where the less polar compounds had the strongest cytotoxicity

Exposure to Anacardiaceae Volatile Oils and Their Constituents Induces Lipid Peroxidation within Food-Borne Bacteria Cells

The chemical composition of the volatile oils from five Anacardiaceae species and their activities against Gram positive and negative bacteria were assessed. The peroxidative damage within bacterial cell membranes was determined through the breakdown product malondialdehyde (MDA). The major constituents in Anacardium humile leaves oil were (E)-caryophyllene (31.0%) and α-pinene (22.0%), and in Anacardium occidentale oil they were (E)-caryophyllene (15.4%) and germacrene-D (11.5%). Volatile oil from Astronium fraxinifolium leaves were dominated by (E)-β-ocimene (44.1%) and α-terpinolene (15.2%), whilst the oil from Myracrodruon urundeuva contained an abundance of δ-3-carene (78.8%). However, Schinus terebinthifolius leaves oil collected in March and July presented different chemical compositions. The oils from all species, except the one from A. occidentale, exhibited varying levels of antibacterial activity against Staphylococcus aureus, Bacillus cereus and Escherichia coli. Oil extracted in July from S. terebinthifolius was more active against all bacterial strains than the corresponding oil extracted in March. The high antibacterial activity of the M. urundeuva oil could be ascribed to its high δ-3-carene content. The amounts of MDA generated within bacterial cells indicate that the volatile oils induce lipid peroxidation. The results suggest that one putative mechanism of antibacterial action of these volatile oils is pro-oxidant damage within bacterial cell membrane explaining in part their preservative properties