Cytotoxic Minor Piericidin Derivatives from the Actinomycete Strain Streptomyces psammoticus SCSIO NS126.
Cytotoxic Minor Piericidin Derivatives from the Actinomycete Strain Streptomyces psammoticus SCSIO NS126.
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DOI：
10.3390/md19080428
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发表时间：
2021-07-28
期刊：
影响因子：
5.4
通讯作者：
Zhou X
中科院分区：
文献类型：
--
作者：
Li K;Su Z;Gao Y;Lin X;Pang X;Yang B;Tao H;Luo X;Liu Y;Zhou X
红树林沉积物来源的放线菌菌株Streptomyces psammoticus SCSIO NS 126被发现具有抗肾细胞癌活性的生产性杀粉蝶菌素代谢产物。在本研究中，为了探索更多样的杀粉蝶菌素衍生物，从而发现上级抗肿瘤先导化合物，在优化的发酵条件下以300-L规模进一步发酵NS 126菌株。结果，获得了八种新的次要杀粉蝶素衍生物（杀粉蝶素L-R（1-7）和11-去甲基-glucopiericidin A（8）），沿着glucopiericidin B（9）。新的结构，包括绝对构型的光谱方法结合实验和计算的电子圆二色性确定。我们还提出了合理的生物合成途径，这些不寻常的后修饰piericidins。化合物1和6对OS-RC-2细胞具有选择性的细胞毒活性，化合物2-5对HL-60细胞具有较强的细胞毒活性，IC 50均小于0.1 μM。新的杀粉蝶素苷8对ACHN、HL-60和K562具有细胞毒性，IC 50值分别为2.3、1.3和5.5 μM。然后进一步研究了1和6在OS-RC-2细胞中、2在HL-60细胞中和8在ACHN细胞中诱导的细胞周期和细胞凋亡效应的阻滞能力。本研究丰富了杀粉蝶菌素衍生物的结构多样性，证实了杀粉蝶菌素作为有前途的抗肿瘤药物值得进一步研究。
The mangrove-sediment-derived actinomycete strain Streptomyces psammoticus SCSIO NS126 was found to have productive piericidin metabolites featuring anti-renal cell carcinoma activities. In this study, in order to explore more diverse piericidin derivatives, and therefore to discover superior anti-tumor lead compounds, the NS126 strain was further fermented at a 300-L scale under optimized fermentation conditions. As a result, eight new minor piericidin derivatives (piericidins L-R (1–7) and 11-demethyl-glucopiericidin A (8)) were obtained, along with glucopiericidin B (9). The new structures including absolute configurations were determined by spectroscopic methods coupled with experimental and calculated electronic circular dichroism. We also proposed plausible biosynthetic pathways for these unusual post-modified piericidins. Compounds 1 and 6 showed selective cytotoxic activities against OS-RC-2 cells, and 2–5 exhibited potent cytotoxicity against HL-60 cells, with IC50 values lower than 0.1 μM. The new piericidin glycoside 8 was cytotoxic against ACHN, HL-60 and K562, with IC50 values of 2.3, 1.3 and 5.5 μM, respectively. The ability to arrest the cell cycle and cell apoptosis effects induced by 1 and 6 in OS-RC-2 cells, 2 in HL-60 cells, and 8 in ACHN cells were then further investigated. This study enriched the structural diversity of piericidin derivatives and confirmed that piericidins deserve further investigations as promising anti-tumor agents.
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