Pyripyropene A

Names

[ Name ]:
Pyripyropene A

[Synonym ]:
Homopurine
1,3,5,7-Tetraazanaphthalene
(3S,4R,4aR,6S,6aS,12R,12aS,12bS)-4-(Acetoxymethyl)-12-hydroxy-4,6a,12b-trimethyl-11-oxo-9-(pyridin-3-yl)-1,3,4,4a,5,6,6a,12,12a,12b-decahydro-2H,11H-benzo[f]pyrano[4,3-b]chromene-3,6-diyl diacetate
(3S,4R,4aR,6S,6aS,12R,12aS,12bS)-4-(Acetoxymethyl)-12-hydroxy-4,6a,12b-trimethyl-11-oxo-9-(3-pyridinyl)-1,3,4,4a,5,6,6a,12,12a,12b-decahydro-2H,11H-benzo[f]pyrano[4,3-b]chromene-3,6-diyl diacetate
2H,11H-Naphtho[2,1-b]pyrano[3,4-e]pyran-11-one, 3,6-bis(acetyloxy)-4-[(acetyloxy)methyl]-1,3,4,4a,5,6,6a,12,12a,12b-decahydro-12-hydroxy-4,6a,12b-trimethyl-9-(3-pyridinyl)-, (3S,4R,4aR,6S,6aS,12R,12aS,12bS)-
pyripropen A
Pyrimidopyrimidin

Biological Activity

[Description]:

Pyripyropene A is a potent and selective sterol O-acyltransferase 2 (SOAT2)/acyl-coenzyme A:cholesterol acyltransferase 2 (ACAT2) inhibitor, with an IC50 of 0.07 µM. Pyripyropene A attenuates hypercholesterolemia and atherosclerosis in vivo[1][2][3][4].

[Related Catalog]:

Research Areas >> Cardiovascular Disease

Research Areas >> Infection

Research Areas >> Inflammation/Immunology

[Target]

IC50: 0.07 µM (ACAT2)[1]

[In Vitro]

Pyripyropene A (0-100 µM; 72 hours) exhibits anti-proliferative activity against HUVECs, and with an IC50 value of 1.8 µM[1]. Pyripyropene A (10 µM ; 24 hours) inhibits VEGF (20 ng/ml)-induced migration and tubular formation of HUVECs in dose-dependent fashion[1]. Pyripyropene A do not show growth inhibitory effects against KB3-1, K562 and Neuro2A cells[1]. Cell Proliferation Assay[1] Cell Line: HUVECs Concentration: 0-100 µM Incubation Time: 72 hours Result: Exhibited anti-proliferative activity against HUVECs with an IC50 value of 1.8 µM.

[In Vivo]

Pyripyropene A (10-50 mg/kg per day; p.o; 12 weeks) reduces the levels of plasma cholesterol, very-low-density lipoprotein (VLDL), and low-density lipoprotein (LDL) and hepatic cholesterol content in apolipoprotein E-knockout mice. And Pyripyropene A-treated mice display reduction of atherogenic lesion areas in the aortae and heart[3]. Pyripyropene A inhibits the hepatic e acyl–coenzyme A:cholesterol acyltransferase 2 (ACAT2) activity in vivo[3]. Pyripyropene A displays a half-life (t1/2) of 0.693/λ, where λ represented the terminal slope of the log-linear portion of concentration time profile[4]. Animal Model: Male C57BL/6 mice[2] Dosage: 0 mg/kg, 1 mg/kg, 10 mg/kg, 50 mg/kg, 100 mg/kg Administration: Oral administration; daily; for 12 weeks Result: Reduced atherogenic lesion areas in the aortae and heart. Animal Model: 9-week old male ICR mice (pharmacokinetic analysis)[4] Dosage: 5 mg/kg ,10 mg/kg Administration: Oral administration Result: t1/2 = 0.693/λ

[References]

[1]. Hayashi A, et al. Pyripyropenes, fungal sesquiterpenes conjugated with alpha-pyrone and pyridine moieties, exhibits anti-angiogenic activity against human umbilical vein endothelial cells. Biol Pharm Bull. 2009 Jul;32(7):1261-5.

[2]. Ohtawa M, et al. Design and Synthesis of A-Ring Simplified Pyripyropene A Analogues as Potent and Selective Synthetic SOAT2 Inhibitors. ChemMedChem. 2018 Mar 6;13(5):411-421.

[3]. Ohshiro T, et al. Pyripyropene A, an acyl-coenzyme A:cholesterol acyltransferase 2-selective inhibitor, attenuates hypercholesterolemia and atherosclerosis in murine models of hyperlipidemia. Arterioscler Thromb Vasc Biol. 2011 May;31(5):1108-15.

[4]. Lee KR , et al. Determination of Penicillium griseofulvum-oriented pyripyropene A, a selective inhibitor of acyl-coenzyme A:cholesterol acyltransferase 2, in mouse plasma using liquid chromatography-tandem mass spectrometry and its application to pharmacokinetic studies. Biomed Chromatogr. 2019 Feb;33(2):e4388.

Chemical & Physical Properties

[ Density]:
1.3±0.1 g/cm3

[ Boiling Point ]:
690.8±55.0 °C at 760 mmHg

[ Melting Point ]:
153-154°C (lit.)

[ Molecular Formula ]:
C₃₁H₃₇NO₁₀

[ Molecular Weight ]:
583.626

[ Flash Point ]:
371.6±31.5 °C

[ Exact Mass ]:
583.241760

[ PSA ]:
151.46000

[ LogP ]:
2.68

[ Vapour Pressure ]:
0.0±2.3 mmHg at 25°C

[ Index of Refraction ]:
1.587

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: QL6289000

CHEMICAL NAME :: 2H,11H-Naphtho(2,1-b)pyrano(3,4-e)pyran-11-one, 1,3,4,4a,5,6a,12,12a,12b-decahydro-4- ((acetyloxy)methyl)-3,6-bis(acetyloxy)-12-hydroxy-9-( 3-pyridinyl)-4,6a,12b -trimethyl-

CAS REGISTRY NUMBER :: 147444-03-9

LAST UPDATED :: 199509

DATA ITEMS CITED :: 1

MOLECULAR FORMULA :: C31-H37-N-O10

MOLECULAR WEIGHT :: 583.69

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: LD - Lethal dose

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: >200 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: 47,148,1994

Related Compounds

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