The use of an HPLC bioactivity profiling/microtiter plate technique in conjunction with capillary probe NMR instrumentation and access to appropriate databases effectively short-circuits conventional dereplication procedures, necessarily based on multimilligram extracts, to a single, more rapid submilligram operation. This approach to dereplication is illustrated using fungal or bacterial extracts that contain known compounds. In each case the dereplication steps were carried out on microgram quantities of extract and demonstrate the discriminating power of (1)H NMR spectroscopy as a definitive dereplication tool.

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The impact of the Tobacco Heating System 2.2 (THS 2.2) on indoor air quality was evaluated in an environmentally controlled room using ventilation conditions recommended for simulating "Office", "Residential" and "Hospitality" environments and was compared with smoking a lit-end cigarette (Marlboro Gold) under identical experimental conditions. The concentrations of eighteen indoor air constituents (respirable suspended particles (RSP) < 2.5 μm in diameter), ultraviolet particulate matter (UVPM), fluorescent particulate matter (FPM), solanesol, 3-ethenylpyridine, nicotine, 1,3-butadiene, acrylonitrile, benzene, isoprene, toluene, acetaldehyde, acrolein, crotonaldehyde, formaldehyde, carbon monoxide, nitrogen oxide, and combined oxides of nitrogen) were measured. In simulations evaluating THS 2.2, the concentrations of most studied analytes did not exceed the background concentrations determined when non-smoking panelists were present in the environmentally controlled room under equivalent conditions. Only acetaldehyde and nicotine concentrations were increased above background concentrations in the "Office" (3.65 and 1.10 μg/m(3)), "Residential" (5.09 and 1.81 μg/m(3)) and "Hospitality" (1.40 and 0.66 μg/m(3)) simulations, respectively. Smoking Marlboro Gold resulted in greater increases in the concentrations of acetaldehyde (58.8, 83.8 and 33.1 μg/m(3)) and nicotine (34.7, 29.1 and 34.6 μg/m(3)) as well as all other measured indoor air constituents in the "Office", "Residential" and "Hospitality" simulations, respectively.

Using HPLC/microtiter-plate-based generation of activity profiles the extract of a marine alga-derived fungus, identified as Gliocladium sp., was shown to contain the known strongly cytotoxic metabolite 4-keto-clonostachydiol (1) and also clonostachydiol (2) as well as gliotide (3), a new cyclodepsipeptide containing several D-amino acids. The absolute configuration of 1 was elucidated by reduction to 2, and two further oxidized derivatives of clonostachydiol (5, 6) were prepared and evaluated for biological activity.

Subinhibitory concentrations of antibiotics were found to enhance and modulate the production of new phenazines, streptophenazines A-H, in a marine Streptomyces isolate. The streptophenazines differ in length and substitution of an alkyl chain. The pattern of metabolites formed depends on the antibiotic used. In the presence of tetracycline, streptophenazines F and G were induced and the production of streptophenazines A-D was increased. When using bacitracin, mainly streptophenazine H was produced. Streptophenazines C and H showed moderate activity against Bacillus subtilis, while streptophenazine C was also active against Staphylococcus lentus.

From cell cultures of Suberites domuncula was isolated a bacterial strain, SDC-1, which was identified by 16S ribosomal RNA sequence analysis as an alpha-Proteobacterium of the genus Ruegeria. The occurrence of the strain in sponge cell culture could be explained by its resistance to the antibiotics used in the isolation of sponge cell cultures or by the preservation of SDC-1 by host sponge cells. The fatty acid composition of SDC-1 is characterized by branched C-12 methyl fatty acids. Two new and 8 known cyclic dipeptides were isolated and characterized from the fermentation broth of SDC-1. Cyclodipeptides are one of the families of cell-cell signaling compounds and may have some role to play in sponge-bacteria interactions.

By the application of an HPLC bioactivity profiling/microtiter technique in conjunction with capillary NMR instrumentation and access to the AntiMarin database the conventional evaluation/isolation dereplication/characterization procedures can be dramatically truncated. This approach is illustrated using the isolation of a new peptaibol, chrysaibol (1), from a New Zealand isolate of the mycoparasitic fungus Sepedonium chrysospermum. The unique nature of chrysaibol was recognized by bioactivity-guided fractionation using HPLC bioactivity profiling/microtiter plate analysis in conjunction with capillary NMR instrumentation and the AntiMarin database. 2D NMR techniques, in combination with MS fragmentation experiments, determined the planar structure of chrysaibol (1), while the absolute configurations of the amino acid residues were defined by Marfey's method. Chrysaibol (1) was cytotoxic against the P388 murine leukemia cell line (IC50 6.61 microM) and showed notable activity against Bacillus subtilis (IC50 1.54 microM).

The synthesis and structure-activity relationships for a series of 14 new avarol derivatives as antioxidants and inhibitors of cell proliferation and PGE(2) generation in human keratinocytes are described. Compound 6 (thiosalicylic derivative) was the most potent inhibitor of superoxide generation in human neutrophils and also potently inhibited PGE(2) generation in the human keratinocyte HaCaT cell line. Compound 7(3'-methylaminoavarone) presented the best antiproliferative profile, by the inhibition of (3)H-thymidine incorporation in HaCaT cells, with potency similar to the reference compound anthralin. None of the avarol derivatives showed any sign of cytotoxicity measured as LDH release in treated keratinocytes. The potency and pharmacological profile of derivatives are also discussed.