Cytotoxicity of Shikonin Metabolites with Biotransformation of Human Intestinal Bacteria
JOURNAL OF MICROBIOLOGY AND BIOTECHNOLOGY(2000)
摘要
Sire shikonin metabolites were obtained from human intestinal bacteria Bacteriodes fragilis subsp. thetaotus, following biotransformation. The transformation of shikonin (1) was performed anaerobically for 3 day at 37 degrees C in the bacterial suspension of B. fragilis which was cultured overnight in GAM broth. The incubation mixture was extracted with EtOAc to give a dark-brown residue. The residue was applied to a silica gel column, which was eluted successively with hexane (Fr. A), CHCl3 (Fr. B), and CHCl3:MeOH (9:1) (Fr. C). Six metabolites, Fr.A (2 and 3), Fr. B (6 and 7), and Fr. C (4 and 5) were isolated by repeated silica gel column chromatography, preparative TLC, followed by Sephadex LH-20. In vitro cytotoxicities were tested against human tumor cell lines; PC-3 (prostate), ACHN (renal), A549 (lung), SW620 (colon), K562 (leukemia), and Du145 (prostate). The shikonin metabolites 2, t, 5, and 6 showed weaker cytotoxicity than the parent shikonin (1), whereas shikonin monomeric metabolite 3 (ED50 0.44-1.22 mu g/ml) and dimeric metabolite 7 (ED50 0.48- 2.35 mu g/ml) exhibited stronger activities compared with adriamycin, which was used as the positive control.
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关键词
shikonin,biotransformation,Bacteriodes fragilis subsp thetaotus,cytotoxicity
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