2-Epi-anthracimycin, a new cytotoxic agent from the marine-derived actinomycete Streptomyces sp. OPMA00631

2-Epi-anthracimycin, a new cytotoxic agent from the marine-derived actinomycete Streptomyces sp. OPMA00631
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DOI:
10.1038/s41429-020-0309-2
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发表时间:
2020-05-13
影响因子:
3.3
通讯作者:
Tomoda, Hiroshi
Tomoda, Hiroshi
中科院分区:
医学4区
文献类型:
--
作者:
Fukuda, Takashi;Nagai, Kenichiro;Tomoda, Hiroshi

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从海洋放线菌Streptomyces sp.OPMA00631的培养液中分离得到一种新的细胞毒活性物质2-表蒽霉素(1),沿着还分离到蒽霉素和蒽霉素B(2-去甲基蒽霉素)。1的结构是基于光谱分析(1D和2D NMR数据和ROESY相关性)来阐明的。化合物1对Jurkat细胞表现出细胞毒性,20小时内的IC 50值为50.5 μ M。研究了1对Jurkat细胞细胞周期分布的影响。化合物1(7.80 μ M)在20小时内使G1期细胞从51.1%增加到62.0%,相反地,使G2和M期细胞从30.7%减少到19.3%。在较高的浓度下,1(250 μ M)显着增加subG 1期细胞(1.9%,0小时至16.5%,20小时),而G1期细胞的比例保持(62.3%)。这些结果表明,1通过将细胞周期阻滞在G1期而对Jurkat细胞表现出细胞毒性。
A new cytotoxic agent designated as 2-epi-anthracimycin (1) was isolated along with anthracimycin and anthracimycin B (2-demethylanthracimycin) from the culture broth of the marine-derived actinomycete Streptomyces sp. OPMA00631. The structure of 1 was elucidated based on spectroscopic analyses (1D and 2D NMR data and ROESY correlations). Compound 1 exhibited cytotoxicity against Jurkat cells with an IC50 value of 50.5 mu M in 20 h. The effect of 1 on the cell cycle distribution of Jurkat cells was investigated. Compound 1 (7.80 mu M) increased G1 phase cells from 51.1 to 62.0% and conversely, decreased G2 and M phase cells from 30.7 to 19.3 % in 20 h. At a higher concentration, 1 (250 mu M) markedly increased subG1 phase cells (1.9% at 0 h to 16.5% at 20 h), while the proportion of G1 phase cells was maintained (62.3%). These results suggest that 1 exhibits cytotoxicity against Jurkat cells by arresting the cell cycle at the G1 phase.