Cerulenin

Title: Cerulenin
CAS Registry Number: 17397-89-6
CAS Name: (2R,3S)-3-[(4E,7E)-1-Oxo-4,7-nonadienyl]oxiranecarboxamide
Additional Names: 2,3-epoxy-4-oxo-7,10-dodecadienamide; 2,3-epoxy-4-oxo-7,10-dodecadienoylamide; helicocerin
Molecular Formula: C12H17NO3
Molecular Weight: 223.27
Percent Composition: C 64.55%, H 7.67%, N 6.27%, O 21.50%
Literature References: Antifungal antibiotic isolated from Cephalosporium caerulens; Acryocylindrium oryzae; Helicoceras oryzae: T. Hata et al., Jpn. J. Bacteriol. 15, 1075 (1960); Matsumae et al., J. Antibiot. 16A, 236, 239 (1963); Sano et al., ibid. 20A, 344 (1967); Furuya, Shirasaka, JP 70 21638 (1970 to Sankyo), C.A. 73, 108271k (1970). Biological characteristics: Matsumae et al., J. Antibiot. 17A, 1 (1964). Structure: Omura et al., ibid. 20A, 349 (1967). Abs config: eidem, Chem. Pharm. Bull. 17, 2361 (1969); Arison, Omura, J. Antibiot. 27, 28 (1974). Stereoselective synthesis of (+)- and (-)-tetrahydrocerulenin and corrected abs config of (+)-cerulenin: H. Ohrui, S. Emoto, Tetrahedron Lett. 1978, 2095; J.-R. Pougny, P. Sinay, ibid. 3301. Stereoselective synthesis of the (+)-form from D-glucose: N. Sueda et al., ibid. 1979, 2039; M. Pietraszkiewicz, P. Sinay, ibid. 4741. Interrupts yeast-type fungi growth by inhibiting the biosynthesis of sterols and fatty acids. Mechanism of action studies: Nomura et al., J. Biochem. 71, 783 (1972); eidem, J. Antibiot. 25, 365 (1972); see also D. Vance, Biochem. Biophys. Res. Commun. 48, 649 (1972). Total synthesis of (±)-cerulenin: R. K. Boeckman, Jr., E.W. Thomas, J. Am. Chem. Soc. 99, 2805 (1977); A. A. Jakubowski et al., Tetrahedron Lett. 1977, 2399; E. J. Corey, D. R. Williams, ibid. 3847; K. Mikami et al., Chem. Lett. 1981, 1721; A. A. Jakubowski et al., J. Org. Chem. 47, 1221 (1982).
Properties: White needles from benzene, mp 93-94°. bp 120° (10-8 mm). [a]D16 +63° (c = 2 in methanol). Stable in neutral and acidic solns. Sol in ethanol, acetone, benzene and most common solvents. Slightly sol in water. Practically insol in petr ether. LD50 in mice (mg/kg): 154 i.v.; 211 i.p.; 547 orally (Matsumae 1964).
Melting point: mp 93-94°
Boiling point: bp 120° (10-8 mm)
Optical Rotation: [a]D16 +63° (c = 2 in methanol)
Toxicity data: LD50 in mice (mg/kg): 154 i.v.; 211 i.p.; 547 orally (Matsumae 1964)
Derivative Type: DL-Form
Properties: mp 40-43°.
Melting point: mp 40-43°
Use: Biochemical tool.
Ceruletide Ceruloplasmin Cervicarcin Cesium Bromide Cesium Carbonate

Cerulenin
Cerulenin.svg
Identifiers
CAS number 17397-89-6 YesY
PubChem 5282054
ChemSpider 4445281 YesY
DrugBank DB01034
KEGG C12058 YesY
ChEBI CHEBI:171741 N
ChEMBL CHEMBL45627 N
Jmol-3D images Image 1
Properties
Molecular formula C12H17NO3
Molar mass 223.27 g mol−1
Density 1.135 g/mL
Boiling point 456.14 °C; 853.05 °F; 729.29 K
 N (verify) (what is: YesY/N?)
Except where noted otherwise, data are given for materials in their standard state (at 25 °C (77 °F), 100 kPa)
Infobox references

Cerulenin is an antifungal antibiotic that inhibits fatty acid and steroid biosynthesis. In fatty acid synthesis, it has been reported to bind in equimolar ratio to b-keto-acyl-ACP synthase, one of the seven moieties of fatty acid synthase, blocking the interaction of malonyl-CoA. It also has the related activity of stimulating fatty acid oxidation through the activation of CPT1, another enzyme normally inhibited by malonyl-CoA. Inhibition involves covalent thioacylation that permanently inactivates the enzymes.[1] These two behaviors may increase the availability of energy in the form of ATP, perhaps sensed by AMPK, in the hypothalamus.[2]

In sterol synthesis, cerulenin inhibits HMG-CoA synthetase activity.[3] It was also reported that cerulenin specifically inhibited fatty acid biosynthesis in Saccharomyces cerevisiae without having an effect on sterol formation.[3] But in general conclusion, cerulenin has inhibitory effects on sterol synthesis.

Cerulenin causes a dose-dependent decrease in HER2/neu protein levels in breast cancer cells, from 14% at 1.25 to 78% at 10 milligrams per liter, and targeting of fatty acid synthase by related drugs has been suggested as a possible treatment.[4] Antiproliferative and pro-apoptotic effects have been shown in colon cells as well.[5] At an intraperitoneal dose of 30 milligrams per kilogram, it has been shown to inhibit feeding and induce dramatic weight loss in mice by a mechanism similar to, but independent or downstream of, leptin signaling.[6] It is found naturally in the industrial strain Cephalosporium caerulens (Sarocladium oryzae, the sheath rot pathogen of rice).