Anake Kijjoa

Naturally-Occurring Xanthones: Recent Developments

A literature survey covering the report of naturally occurring xanthones from January 2000 to December 2004, with 219 references, is presented in this review. Among 515 xanthones reported in this period, 278 were new natural xanthones. These xanthones have been identified from 20 families of higher plants (122 species in 44 genera), fungi (19 species) and lichens (3 species). The structural formulas of 368 identified xanthones, their distribution and a brief mention of their biological properties are also included.

Protoberberine alkaloids from Coscinium fenestratum

Abstract Stems of Coscinium fenestratum from Thailand furnished the new protoberberine alkaloids oxypalmatine, (−)-8- oxotetrahydrothalifendine, (−)-8-oxoisocorypalmine and either (−)-8-oxothaicanine or (−)-8-oxo-3-hydroxy-2,4, 9,10-tetramethoxyberbine in addition to berberine, the major alkaloid and (−)-8-oxocanadine.

Can Some Marine-Derived Fungal Metabolites Become Actual Anticancer Agents?

Marine fungi are known to produce structurally unique secondary metabolites, and more than 1000 marine fungal-derived metabolites have already been reported. Despite the absence of marine fungal-derived metabolites in the current clinical pipeline, dozens of them have been classified as potential chemotherapy candidates because of their anticancer activity. Over the last decade, several comprehensive reviews have covered the potential anticancer activity of marine fungal-derived metabolites. However, these reviews consider the term “cytotoxicity” to be synonymous with “anticancer agent”, which is not actually true. Indeed, a cytotoxic compound is by definition a poisonous compound. To become a potential anticancer agent, a cytotoxic compound must at least display (i) selectivity between normal and cancer cells (ii) activity against multidrug-resistant (MDR) cancer cells; and (iii) a preferentially non-apoptotic cell death mechanism, as it is now well known that a high proportion of cancer cells that resist chemotherapy are in fact apoptosis-resistant cancer cells against which pro-apoptotic drugs have more than limited efficacy. The present review thus focuses on the cytotoxic marine fungal-derived metabolites whose ability to kill cancer cells has been reported in the literature. Particular attention is paid to the compounds that kill cancer cells through non-apoptotic cell death mechanisms.

The in vitro anticancer activity of the crude extract of the sponge-associated fungus Eurotium cristatum and its secondary metabolites

Background: Marine natural products has captivated many researchers over the years and there is always a need for sources of diverse and pharmacologically active leads in the area of anticancer drugs. Materials and Methods: The ethyl acetate extract of the fungus Eurotium cristatum (ECE), isolated from the marine sponge Mycale sp., furnished 2-(2’, 3-epoxy-1’,3’-heptadienyl)-6-hydroxy-5-(3-methyl-2-butenyl) benzaldehyde (1), 1,8-dihydroxy-6-methoxy-3-methyl-9,10-anthracenedione (physcion, 2), and the dioxopiperazine alkaloid echinulin (3). The structures of the compounds were established by Nuclear Magnetic Resonance (NMR) spectral analysis (1H, 13C, DEPT, COSY, HSQC, and HMBC). The ECE and its metabolites were evaluated for their growth inhibitory activity on the following three human tumor cell lines: breast adenocarcinoma (MCF-7), non-small lung cancer (NCI-H460), and melanoma (A375-C5). Results: The results showed that the ECE was active in all the three cell lines, with the values of GI50 = 44.3 ± 1.2, 45.5 ± 7.5, and 71.3 ± 2.1 μg/ml for MCF-7, NCI-H460, and A375-C5, respectively. Compound 1 also exhibited moderate growth inhibitory activity against all the three cell lines (GI50 = 58.3 ± 1.2, 46.0 ± 5.5, and 116.7 ± 7.2 μM for MCF-7, NCI-H460, and A375-C5, respectively), whereas compound 3 showed only weak inhibition against MCF-7 (GI50 = 109.7 ± 0.3 μM) and NCI-H460 (GI50 = 96.7 ± 1.5 μM) but was inactive against A375-C5 (GI50 >150 μM). On the contrary, compound 2 was inactive in all the three cell lines at the highest concentration tested (150 μM). Furthermore, ECE was investigated for its effect on the cell cycle in the NCI-H460 cells. Analysis of the cell cycle profile showed that ECE was able to cause a slight cell arrest in the G1 phase, with a corresponding decrease of cells in the S and G2/M phases. Conclusion: The secondary metabolites isolated [Compound 1] from the crude ethyl acetate extract of the culture of the marine fungus E. cristatum were found as the most potent compound regarding cell growth inhibition.

Xanthones from Cratoxylum maingayi

Abstract 1,7-dihydroxy-, 2,8-dihydroxy-1-methoxy-, 1,7-dihydroxy-4-methoxyxanthone and the new 7-hydroxy-1,2,3,8-tetramethoxyxanthone, were isolated from the wood of Cratoxylum maingayi. The structure of the new xanthone was confirmed by X-ray crystallography.

Clerodane derivatives from Polyalthia viridis

Abstract The non-polar fraction of a methanol extract of Polyalthia viridis bark furnished methyl farnesoate, 3,13 E - kolavadien-15-oic acid, a new clerodane, a new bisnorclerodane and a new modified clerodane with a rearranged carbon skeleton.

Antibacterial and Antibiofilm Activities of Tryptoquivalines and Meroditerpenes Isolated from the Marine-Derived Fungi Neosartorya paulistensis, N. laciniosa, N. tsunodae, and the Soil Fungi N. fischeri and N. siamensis

A new meroditerpene, sartorypyrone C (5), was isolated, together with the known tryptoquivalines l (1a), H (1b), F (1c), 3′-(4-oxoquinazolin-3-yl) spiro[1H-indole-3,5′]-2,2′-dione (2) and 4(3H)-quinazolinone (3), from the culture of the marine sponge-associated fungus Neosartorya paulistensis (KUFC 7897), while reexamination of the fractions remaining from a previous study of the culture of the diseased coral-derived fungus N. laciniosa (KUFC 7896) led to isolation of a new tryptoquivaline derivative tryptoquivaline T (1d). Compounds 1a–d, 2, 3, and 5, together with aszonapyrones A (4a) and B (4b), chevalones B (6) and C (7a), sartorypyrones B (7b) and A (8), were tested for their antibacterial activity against four reference strains (Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Pseudomonas aeruginosa), as well as the environmental multidrug-resistant isolates. Only aszonapyrone A (4a) and sartorypyrone A (8) exhibited significant antibacterial activity as well as synergism with antibiotics against the Gram-positive multidrug-resistant strains. Antibiofilm assays of aszonapyrone A (4a) and sartorypyrone A (8) showed that practically no biofilm was formed in the presence of their 2× MIC and MIC. However, the presence of a sub-inhibitory concentration of ½ MIC of 4a and 8 was found to increase the biofilm production in both reference strain and the multidrug-resistant isolates of S. aureus.

Stilbenes and other constituents of Knema austrosiamensis.

Abstract The wood of Knema austrosiamense furnished the resveratrol derivatives 3,4′-dimethoxy-5-hydroxystilbene and 3,5-dihydroxy-4′-methoxystilbene, 1-(2-methoxy-4-hydroxyphenyl) 3-(3-hydroxy-4-methoxyphenyl)-propane, three acylresorcinols, three acylphloroglucinols, (+)-episesamin, (+)-xanthoxylol and (±)-7,4′-dihydroxy-3′-methoxyflavan.

Inhibition of lymphocyte proliferation by prenylated flavones: artelastin as a potent inhibitor.

Eight natural prenylated flavones, previously isolated from Artocarpus elasticus, were evaluated for their effect on the mitogenic response of human lymphocytes to PHA. They all exhibited a dose-dependent suppression effect. An interesting relationship was observed between their antiproliferative activity and their chemical structure. Indeed, the most potent flavones possessed a 3,3-dymethylallyl group (prenyl) at C-8, such as artelastin, which exhibited the highest antiproliferative activity. Studies of the mechanism underlying its effect revealed that artelastin had an irreversible inhibitory effect on the PHA-induced lymphocyte proliferation and could affect the course of the ongoing mitogenic response either at the initial induction phase or at the late phase of proliferation. This prenylated flavone was also shown to be a potent inhibitor of both T- and B-lymphocyte mitogen induced proliferation although B-mitogenic response was the more sensitive one. Artelastin did not affect either the basal levels of the early marker of activation CD69 on non-stimulated splenocytes or its expression on ConA- or LPS-stimulated splenocytes. However, it decreased the production of IFN-gamma, IL-2, IL-4 and IL-10 in ConA-stimulated splenocytes. Furthermore, artelastin had no effect on apoptosis of splenocytes.

A new cyclic hexapeptide and a new isocoumarin derivative from the marine sponge-associated fungus Aspergillus similanensis KUFA 0013.

A new isocoumarin derivative, similanpyrone C (1), a new cyclohexapeptide, similanamide (2), and a new pyripyropene derivative, named pyripyropene T (3) were isolated from the ethyl acetate extract of the culture of the marine sponge-associated fungus Aspergillus similanensis KUFA 0013. The structures of the compounds were established based on 1D and 2D NMR spectral analysis, and in the case of compound 2 the stereochemistry of its amino acid constituents was determined by chiral HPLC analysis of the hydrolysate by co-injection with the d and l amino acids standards. Compounds 2 and 3 were evaluated for their in vitro growth inhibitory activity against MCF-7 (breast adenocarcinoma), NCI-H460 (non-small cell lung cancer) and A373 (melanoma) cell lines, as well as antibacterial activity against reference strains and the environmental multidrug-resistant isolates (MRS and VRE). Only compound 2 exhibited weak activity against the three cancer cell lines, and neither of them showed antibacterial activity.