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

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.

Marine-Derived Piericidin Diglycoside S18 Alleviates Inflammatory Responses in the Aortic Valve via Interaction with Interleukin 37

“…Accumulating evidence suggests that natural piericidins obtained from marine-derived Streptomyces have received considerable attention in recent years because of their important medicinal activities [23,24]. Our group has previously obtained 43 natural piericidins from two strains of marine-derived Streptomyces, including 29 new compounds [25][26][27], and found that the main piericidin metabolites, including piericidin A (PA) and glucopiericidin A (GPA), have the potential to be developed as potential antirenal carcinoma drugs. Mechanistic studies have shown that these piericidins, whether aglycones or glycosides, could reduce ROS levels and regulate oxidative stress, as inhibitors of mitochondrial respiratory chain complex I. Piericidins can inhibit NF-κB activation by forcing the antioxidative protein peroxiredoxin 1 (PRDX1) into the nucleus [25].…”

Butenolides from the Coral-Derived Fungus Aspergillius terreus SCSIO41404

“…The structures of 1a , 1b , 2a , and 2b were subjected to random conformational searches using the Spartan’14 software with the MMFF method, as used previously [ 23 ]. The conformers with a Boltzmann population of over 5% were chosen for ECD calculations using the Gaussian 09 software [ 24 ], and the stable conformers were initially optimized at the B3LYP/6-31+G(d,p) level in MeOH using the CPCM model.…”

Diversified Chaetoglobosins from the Marine-Derived Fungus Emericellopsis sp. SCSIO41202

“…The overall theoretical calculation of the ECD was achieved in MeOH using time-dependent density functional theory at the B3LYP/6-31+G (d, p) level for the stable conformers of 1 . The ECD spectra of the different conformers were generated using SpecDis 1.6 (University of Würzburg) and Prism 5.0 (GraphPad Software Inc., San Diego, CA, USA) software, with a half-bandwidth of 0.3−0.4 eV, according to the Boltzmann-calculated contribution of each conformer after UV correction [ 29 ].…”