Trichiol and 3-epitrichiol acetate, novel cytotoxic sterols with an unprecedented 2,6-dioxabicyclo[2.2.2]octan-3-one ring system from the myxomycete Trichia favoginea var. persimilis

Trichiol (1) and 3-epitrichiol acetate (2), two new sterols, have been isolated from field-collected fruit bodies of the myxomycete, Trichia favoginea var. persimilis, and their structures elucidated by spectral data. Trichiol (1) and 3-epitrichiol acetate (2) possess an unprecedented 2,6-dioxabicyclo[2.2.2]octan-3-one ring system. Trichiol (1) was cytotoxic against HeLa cells, while compound 2 proved to exhibit reversal effect against TNF-related apoptosis inducing ligand (TRAIL)-resistant Jurkat cell lines.     

Kehokorins A-C, novel cytotoxic dibenzofurans isolated from the myxomycete Trichia favoginea var. persimilis

Kehokorins A (1)-C (3), three novel dibenzofurans, have been isolated from field-collected fruit bodies of the myxomycete, Trichia favoginea var. persimilis, and their structures were elucidated by spectral data. Kehokorin A (1) was a α-l-rhamnopyranoside of kehokorin B (2), while kehokorin C (3) was a 1-demethoxy analog of 2. Kehokorin A (1) was cytotoxic against HeLa cells with an IC₅₀ value of 1.5 μg/mL.     

An analytical method for irinotecan (CPT-11) and its metabolites using a high-performance liquid chromatography: parallel detection with fluorescence and mass spectrometry

Irinotecan or 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin (CPT-11) is an anticancer pro-drug used in the treatment of many types of cancer. We describe here the validation of an analytical method for CPT-11 and its metabolites, including an active metabolite, 7-ethyl-10-hydroxycamptothecin (SN-38), its glucuronidated form, SN-38G, and several cytochrome P450 3A-mediated products such as 7-ethyl-10-[4-N-(5-aminopentanoic acid)-1-piperidino]carbonyloxycamptothecin (APC) using a high-performance liquid chromatography connected to parallel fluorescence and mass spectrometry detection systems. This method is characterized as follows: (1) simple extraction of the analytes from biomaterials with perchloric acid/methanol; (2) sensitive quantitation of major metabolites (SN-38G, SN-38 and APC) with a fluorescence detector (FLD), where the limits of quantitation by FLD were 2.5 ng/mL for SN-38G and APC, 5 ng/mL for CPT-11 and 1 ng/mL for SN-38, respectively; (3) parallel selective monitoring of the metabolites including minor metabolites with a mass selected detector (MSD). There was no observed interference by other drugs expected to be co-administered. This method showed its usefulness by identifying a novel metabolite produced in human hepatic microsomes. The results indicate that this combination of FLD and MSD enables a highly selective analysis of CPT-11 and its metabolites, and is useful for studies both in vivo and in vitro.     

Effects of food on bioavailability of two indomethacin capsules containing different sizes of particles

Two different indomethacin capsules, a commercial one containing fine drug particles and an experimental capsule containing 125-177 microns particles, were employed in this study. The commercial preparation showed faster in vitro dissolution than the experimental one. When administered to humans having normal acidity of the gastric juices, the commercial capsule exhibited higher Cmax and smaller Tmax and mean residence time (MRT) than the experimental one both in fasting and nonfasting states, although the two capsules were equivalent in area under the serum concentration-time curve (AUC). The ingestion of a breakfast delayed the gastrointestinal absorption from both preparations, which resulted in larger Tmax's and MRT's and smaller Cmax's in the nonfasting state. Food, however, did not have any significant effect on the AUC's of the preparations.     

Quantitative in vitro bioassay for recombinant human interleukin-11

A cell culture-based in vitro bioassay was developed to measure the biological activity of recombinant human interleukin-11 (rhIL-11). The bioassay measures induced proliferation of T10 cells, derived from the T1165 murine plasmacytoma line. A colorimetrically detectable formazan product, obtained by cellular reduction of the tetrazolium compound, 4-[3-(4-iodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate (WST-1), was used as an endpoint for response of clone T10 to added rhIL-11. Positions of the samples and the standards in 96-well microplates affected the precision of this bioassay, which was improved by using 2 microplates where serially diluted sample and standard lines were interleaved and their positions were alternated. The coefficient of variation for this bioassay was less than 8%. This method is suitable for quality control of rhIL-11 because of its simplicity, reproducibility, and accuracy.