Piericidins

Piericidins

Catalog Product Name CAS Number Molecular Formula Molecular Weight
BADC-00810 Glucopiericidin A 108073-65-0 C31H47NO9 577.71 g/mol

Piericidins are natural products that are largely produced by Streptomyces species isolated from soil, marine and insect samples in the symbiotic interaction. As a large family of microbial metabolites, Piericidins consist of main skeleton of 4-pyridinol with methylated polyketide side chain. Nonetheless, these metabolites show differences in their bioactive potentials against tumour cells, insects and micro-organisms. Due to its close structural similarity with coenzyme Q, Piericidins also possess an inhibitory activity against ubiquinone oxidoreductase (NADH) dehydrogenase as well as Photosystem II.

Chemical structure

Piericidins consist of an α-pyridone ring linked to an unsaturated linear polyketide chain while showing high structural similarities to coenzyme Q. These resemblances, in turn, enable them to act as NADH-ubiquinone oxidoreductase (complex I) inhibitors and exhibit insecticide activity. The analogues of Piericidins are mainly divided into different categories according to their different C-10 substituents, C-11, C-12 double bonds and epoxy structures (eg, Piericidin A, Piericidin B, Piericidin C, Piericidin D and Piericidin E). Furthermore, when the 10-O-β-D- glucose and 3'-O-β-D-glucose of Piericidin A was glycosylated, two Piericidin glycosides (Glucopiericidin A and Glucopiericidin B) were obtained. Among them, Glucopiericidin A display antimicrobial properties and in vitro inhibitory activity against antibody formation.

Mechanism of action

The Piericidins anti-tumor mechanism is that it can inhibits the expression of Glucose-Regulated Protein 78 (GRP78) of endoplasmic reticulum, which can decrease the resistance of tumor cells and inhibiting the activities of tumor cell growth. Furthermore, Piericidins A and Glucopiericidin A can play a concerted mechanism in inhibiting filopodia protrusion. The mechanism indicated that Glucopiericidin A can inhibit glycolysis through glucose transporter as a target after Piericidins A exerts the inhibitory effect of mitochondrial respiration, which can inhibit the growth of filopodia by reducing intracellular ATP. In the research of human epidermal carcinoma A431 cells, Piericidins can expresses epidermal growth factor receptor (EGF receptor) in high quantity, resulting in cell growth chemotaxis.

Application

Anti-tumour activity of Piericidins was first reported in 1993 through screening the broth culture of Streptomyces to identify new novel phosphatidylinositol turnover inhibitors. Many researches have proved that Piericidin A has inhibitory activity on human oral epidermal cancer cells, chronic leukemia cells, adenovirus-mediated rat glial cells, mouse-derived neuroblastoma cells and mouse lymphocytic leukemia cells. In addition, Piericidin A has selective cytotoxicity to human multiple myeloma cells and colorectal cancer cell line, but had no effect on normal cell growth. Similarly, other analogues and their glycosides also showed cytotoxicity to many cancer cell lines. Such as, Glucopiericidin A has inhibitory activity against human cervical cancer, mouse melanoma, human lung cancer, mouse leukemia cells, and doxorubicin/adriamycin resitance mouse leukemia cells.

References

  1. Sepideh, M.; et al. Biological insights into the piericidin family of microbial metabolites. J. Appl. Microbiol, 2021, 00: 1-13.
  2. Shaaban, K.A.; et al. Glucopiericidin C: a cytotoxic piericidin glucoside antibiotic produced by a marine Streptomyces isolate. The Journal of Antibiotics, 2011, 64: 205-209.
* Only for research. Not suitable for any diagnostic or therapeutic use.

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