Cytotoxic Minor Piericidin Derivatives from the Actinomycete Strain Streptomyces psammoticus SCSIO NS126

作者：Li, Kunlong; Su, Ziqi; Gao, Yongli; Lin, Xiuping; Pang, Xiaoyan; Yang, Bin; Tao, Huaming; Luo, Xiaowei^*; Liu, Yonghong^*; Zhou, Xuefeng^*

来源：Marine Drugs, 2021, 19(8): 428.

DOI：10.3390/md19080428

• actinomycete
• piericidins
• absolute configuration
• cytotoxicity

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 mu M. The new piericidin glycoside 8 was cytotoxic against ACHN, HL-60 and K562, with IC50 values of 2.3, 1.3 and 5.5 mu M, 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.

• 单位
  中国科学院研究生院; 南方医科大学