P-39 ゲノム・メタボローム解析を活用したマクロリド産生渦鞭毛藻の探索と新規抗腫瘍性マクロリドIriomoteolide類の構造(ポスター発表の部)

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Marine dinoflagellates Amphidinium species are known as producers of unique secondary metabolites. In our continuing investigation for new anticancer drug leads from the dinoflagellate Amphidinium sp., we have resulted in the discovery of a new Amphidinium strain producing unknown cytotoxic macrolides, and the isolation of novel cytotoxic macrolides from this strain. From 263 Amphidinium strains isolated from benthic or free-swimming sources collected off South-East Islands. Japan, the HYA024 strain with the ability producing novel cytotoxic macrolides were discovered by using the genomics and metabolomics analyses. The algal cells obtained from the culture were extracted with MeOH/toluene. The toluene-soluble fractions of the extract were subjected to SiO_2 gel, C_<18>, and then NH_2-SiO_2 columns. Macrolide-containing fractions were separated by C_<18> HPLC to afford iriomoteolides-1a (1) and 1b (2). Structure elucidations of 1 and 2 were carried out using detailed analyses of 2D NMR spectra. The relative and absolute stereochemistries were assigned by the combination of conformational analyses using NMR data and modified Mosher's method of 1. On the other hand, the structure of 2 was elucidated on the basis of the spectral data and the conversion reaction from 1 to 2. Iriomoteolides-1a (1) and 1b (2) are 20-membered macrolides having a novel carbon skeleton. Iriomoteolide-1a (1) exhibited potent cytotoxicity against human B lymphocyte DG-75 cells (IC_<50>: 0.002μg/mL), while the IC_<50> value (0.9μg/mL) of 2 against DG-75 cells is ca. 500 times less potent than that of 1. This result suggests that the presence of the 6-membered hemiacetal ring and/or the exomethylene unit in 1 is important for the potent cytotoxicity for 1.
天然有機化合物討論会の論文
2007-08-24

P-39 ゲノム・メタボローム解析を活用したマクロリド産生渦鞭毛藻の探索と新規抗腫瘍性マクロリドIriomoteolide類の構造(ポスター発表の部)

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