Piericidin A  (Synonyms: AR-054)

Piericidin A (AR-054) is a natural mitochondrial NADH-ubiquinone oxidoreductase (complex I) inhibitor. Piericidin A is a potent neurotoxin and inhibits mitochondrial respiration by disrupting the electron transport system through its action on NADH-ubiquinone reductase. Piericidin A is also a potential quorum-sensing inhibitor that suppresses the expression of the virulence genes of Erwinia carotovora subsp. atroseptica (Eca). Piericidin A is an ADC cytotoxin and has anti-bacterial, anticancer, insecticidal activity^[1][2][2].

In a cell free assay, the potency of Piericidin A to inhibit mitochondrial complex I is ∼2 fold smaller than the one of annonacin. In cultured neurons, Piericidin A potently induces the redistribution of phosphorylated tau from the dendrites into the cell soma and induces cell death^[1].
The viability of Tn5B1-4 cells is inhibited by Piericidin A in a time- and concentration-dependent manner with IC₅₀ value of 0.061 μM, whilst Piericidin A shows slight inhibitory effect on the viability of HepG2 and Hek293 cells with IC₅₀ value of 233.97 μM and 228.96 μM, respectively. Piericidin A induces apoptosis of Tn5B1-4 cells coincides with a decrease in the mitochondrial membrane potential^[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Piericidin A (0.5 mg/kg/d; for 28 days via osmotic minipumps) significantly increases the number of phospho-tau immunoreactive cells in the cerebral cortex in P301S^+/+ mice. Piericidin A leads to increased levels of pathologically phosphorylated tau only in P301S^+/+ mice. The synaptic density is reduced by Piericidin A treatment in P301S^+/+ mice. Exposure to Piericidin A aggravates the course of genetically determined tau pathology^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

415.57

C₂₅H₃₇NO₄

2738-64-9

Liquid

Colorless to light yellow

COC1=C(C(C)=C(N=C1OC)C/C=C(C/C=C/C(C)=C/[C@@H](C)[C@H](/C(C)=C/C)O)\C)O

Room temperature in continental US; may vary elsewhere.

Solution, -20°C, 2 years

• [1]. Matthias Höllerhage, et al. Piericidin A Aggravates Tau Pathology in P301S Transgenic Mice. PLoS One. 2014 Dec 1;9(12):e113557.  [Content Brief]

  [2]. Ji Eun Kang, et al. Efficacies of Quorum Sensing Inhibitors, Piericidin A and Glucopiericidin A, Produced by Streptomyces Xanthocidicus KPP01532 for the Control of Potato Soft Rot Caused by Erwinia Carotovora Subsp. Atroseptica. Microbiol Res. 2016 Mar;184:32-41.  [Content Brief]

  [3]. Solange Muhayimana, et al. Cytotoxic Selectivity and Apoptosis Induction of Piericidin A Contributes Potentially to Its Insecticidal Effect Against Mythimna Separata (Lepidoptera: Noctuidae) Larvae. Pestic Biochem Physiol. 2019 Jun;157:19-25.  [Content Brief]