Piericidin A1

Names

[ Name ]:
Piericidin A1

[Synonym ]:
Piericidin A1
2-[(2E,5E,7E,9R,10R,11E)-10-Hydroxy-3,7,9,11-tetramethyl-2,5,7,11-tridecatetraen-1-yl]-5,6-dimethoxy-3-methyl-4(1H)-pyridinone
4(1H)-Pyridinone, 2-[(2E,5E,7E,9R,10R,11E)-10-hydroxy-3,7,9,11-tetramethyl-2,5,7,11-tridecatetraen-1-yl]-5,6-dimethoxy-3-methyl-
2-[(2E,5E,7E,9R,10R,11E)-10-hydroxy-3,7,9,11-tetramethyltrideca-2,5,7,11-tetraen-1-yl]-5,6-dimethoxy-3-methylpyridin-4-ol
piericidin a

Biological Activity

[Description]:

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].

[Related Catalog]:

Research Areas >> Cancer

Research Areas >> Infection

Signaling Pathways >> Antibody-drug Conjugate >> ADC Cytotoxin

Research Areas >> Neurological Disease

Signaling Pathways >> Anti-infection >> Bacterial

[In Vitro]

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].

[In Vivo]

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].

[References]

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

[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.

[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.

Chemical & Physical Properties

[ Density]:
1.1±0.1 g/cm3

[ Boiling Point ]:
591.7±50.0 °C at 760 mmHg

[ Molecular Formula ]:
C₂₅H₃₇NO₄

[ Molecular Weight ]:
415.566

[ Flash Point ]:
311.6±30.1 °C

[ Exact Mass ]:
415.272247

[ PSA ]:
71.81000

[ LogP ]:
4.26

[ Vapour Pressure ]:
0.0±3.8 mmHg at 25°C

[ Index of Refraction ]:
1.534

[ Storage condition ]:
2-8°C

MSDS

Click to get detail MSDS

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: YD4588000

CHEMICAL NAME :: 2,6,9,11-Tridecatetraen-4-ol, 13-(4-hydroxy-5,6-dimethoxy-3-methyl-2-pyridyl)-3,5,7 ,11- tetramethyl-, (all-E)-(4S,5S)-

CAS REGISTRY NUMBER :: 2738-64-9

LAST UPDATED :: 199612

DATA ITEMS CITED :: 5

MOLECULAR FORMULA :: C25-H37-N-O4

MOLECULAR WEIGHT :: 415.63

WISWESSER LINE NOTATION :: T6NJ B2UY1&1U2Y1&U1Y1&YQY1&U2 C1 DQ EO1 FO1

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 360 ug/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: ABCHA6 Agricultural and Biological Chemistry. (Maruzen Co. Ltd., POB 5050, Tokyo International, Tokyo 100-31, Japan) V.25- 1961- Volume(issue)/page/year: 34,1101,1970

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 3170 ug/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: ABCHA6 Agricultural and Biological Chemistry. (Maruzen Co. Ltd., POB 5050, Tokyo International, Tokyo 100-31, Japan) V.25- 1961- Volume(issue)/page/year: 32,1115,1968

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Administration onto the skin

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 2520 ug/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: ABCHA6 Agricultural and Biological Chemistry. (Maruzen Co. Ltd., POB 5050, Tokyo International, Tokyo 100-31, Japan) V.25- 1961- Volume(issue)/page/year: 32,1115,1968

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 870 ug/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: ABCHA6 Agricultural and Biological Chemistry. (Maruzen Co. Ltd., POB 5050, Tokyo International, Tokyo 100-31, Japan) V.25- 1961- Volume(issue)/page/year: 27,576,1963

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 1 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: JANTAJ Journal of Antibiotics. (Japan Antibiotics Research Assoc., 2-20-8 Kamiosaki, Shinagawa-ku, Tokyo, 141, Japan) V.2-5, 1948-52; V.21- 1968- Volume(issue)/page/year: 40,149,1987

Safety Information

[ Personal Protective Equipment ]:
Eyeshields;Faceshields;full-face respirator (US);Gloves;multi-purpose combination respirator cartridge (US);type ABEK (EN14387) respirator filter

[ Hazard Codes ]:
T+

[ Risk Phrases ]:
26/27/28-20/21/22

[ Safety Phrases ]:
28-36/37-45

[ RIDADR ]:
UN 3382 6.1/PG 1

Articles

Isolation and characterizations of quinone analogue-resistant mutants of bo-type ubiquinol oxidase from Escherichia coli.

Biochemistry 37(37) , 12744-52, (1998)

Cytochrome bo is a member of the heme-copper terminal oxidase superfamily and serves as a four-subunit ubiquinol oxidase in the aerobic respiratory chain of Escherichia coli. To probe the location and...

Etoposide-resistant HT-29 human colon carcinoma cells during glucose deprivation are sensitive to piericidin A, a GRP78 down-regulator.

J. Cell Physiol. 215(1) , 243-50, (2008)

Glucose deprivation, a pathophysiological cell condition, causes up-regulation of GRP78 and induction of etoposide resistance in human cancer cells. The induction of drug resistance can be partly expl...

Genetic evidence for the existence of two quinone related inhibitor binding sites in NADH-CoQ reductase.

Biochim. Biophys. Acta 1319(1) , 1-4, (1997)

Using the NADH-CoQ reductase of Rhodobacter capsulatus as a model for the mitochondrial Complex I, we have for the first time isolated bacterial mutants resistant to piericidin-A, a classical inhibito...