2. Academic Validation
  3. Cytotoxic Minor Piericidin Derivatives from the Actinomycete Strain Streptomyces psammoticus SCSIO NS126

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

  • Mar Drugs. 2021 Jul 28;19(8):428. doi: 10.3390/md19080428.
Kunlong Li 1 2 3,  Ziqi Su 4,  Yongli Gao 2 5,  Xiuping Lin 1,  Xiaoyan Pang 1,  Bin Yang 1 2,  Huaming Tao 4,  Xiaowei Luo 6,  Yonghong Liu 1 2 3 6,  Xuefeng Zhou 1 2
Affiliations

Affiliations

  • 1 CAS Key Laboratory of Tropical Marine Bio-Resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, China.
  • 2 Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou), Guangzhou 511458, China.
  • 3 College of Earth and Planetary Sciences, University of Chinese Academy of Sciences, Beijing 100049, China.
  • 4 School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China.
  • 5 Institutional Center for Shared Technologies and Facilities, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, China.
  • 6 Institute of Marine Drugs, Guangxi University of Chinese Medicine, Nanning 530200, China.
PMID: 34436267 DOI: 10.3390/md19080428
Abstract

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.

Keywords

absolute configuration; actinomycete; cytotoxicity; piericidins.

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