Cerulenin
Names
Preferred IUPAC name
(2R,3S)-3-[(4E,7E)-Nona-4,7-dienoyl]oxirane-2-carboxamide
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
DrugBank
ECHA InfoCard 100.037.643 Edit this at Wikidata
KEGG
UNII
  • InChI=1S/C12H17NO3/c1-2-3-4-5-6-7-8-9(14)10-11(16-10)12(13)15/h2-3,5-6,10-11H,4,7-8H2,1H3,(H2,13,15)/b3-2+,6-5+/t10-,11-/m1/s1 checkY
    Key: GVEZIHKRYBHEFX-NQQPLRFYSA-N checkY
  • InChI=1/C12H17NO3/c1-2-3-4-5-6-7-8-9(14)10-11(16-10)12(13)15/h2-3,5-6,10-11H,4,7-8H2,1H3,(H2,13,15)/b3-2+,6-5+/t10-,11-/m1/s1
    Key: GVEZIHKRYBHEFX-NQQPLRFYBP
  • O=C(CC/C=C/C/C=C/C)[C@H]1O[C@H]1C(=O)N
Properties
C12H17NO3
Molar mass 223.2695
Density 1.135 g/mL
Boiling point 456.14 °C (853.05 °F; 729.29 K)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
☒N verify (what is checkY☒N ?)

Cerulenin is an antifungal antibiotic that inhibits fatty acid and steroid biosynthesis. It was the first natural product antibiotic known to inhibit lipid synthesis.[1] 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.[2] These two behaviors may increase the availability of energy in the form of ATP, perhaps sensed by AMPK, in the hypothalamus.[3]

In sterol synthesis, cerulenin inhibits HMG-CoA synthetase activity.[4] It was also reported that cerulenin specifically inhibited fatty acid biosynthesis in Saccharomyces cerevisiae without having an effect on sterol formation.[4] But in general conclusion, cerulenin has inhibitory effects on sterol synthesis.[citation needed]

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.[5] Antiproliferative and pro-apoptotic effects have been shown in colon cells as well.[6] 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.[7] It is found naturally in the industrial strain Cephalosporium caerulens (Sarocladium oryzae, the sheath rot pathogen of rice).[citation needed]

See also

References

  1. ^ Volpe, J J; Vagelos, P R (1976). "Mechanisms and regulation of biosynthesis of saturated fatty acids". Physiological Reviews. 56 (2). American Physiological Society: 339–417. doi:10.1152/physrev.1976.56.2.339. ISSN 0031-9333. PMID 6981.
  2. ^ Straub SG, Yajima H, Komatsu M, Aizawa T, Sharp GW (February 2002). "The effects of cerulenin, an inhibitor of protein acylation, on the two phases of glucose-stimulated insulin secretion". Diabetes. 51 Suppl 1 (90001): S91–5. doi:10.2337/diabetes.51.2007.S91. PMID 11815464.
  3. ^ Reviewed in Ronnett GV, Kleman AM, Kim EK, Landree LE, Tu Y (August 2006). "Fatty acid metabolism, the central nervous system, and feeding". Obesity (Silver Spring). 14 (Suppl 5): 201S–207S. doi:10.1038/oby.2006.309. PMID 17021367.
  4. ^ a b Ohno T, Awaya J, Kesado T, Nomura S, Omura S (October 1974). "Mechanism of Action of CM-55, a Synthetic Analogue of the Antilipogenic Antibiotic Cerulenin". Antimicrob. Agents Chemother. 6 (4): 387–92. doi:10.1128/aac.6.4.387. PMC 444657. PMID 4157441.
  5. ^ Menendez JA, Vellon L, Mehmi I, et al. (July 2004). "Inhibition of fatty acid synthase (FAS) suppresses HER2/neu (erbB-2) oncogene overexpression in cancer cells". Proc. Natl. Acad. Sci. U.S.A. 101 (29): 10715–20. Bibcode:2004PNAS..10110715M. doi:10.1073/pnas.0403390101. PMC 490000. PMID 15235125.
  6. ^ Huang P, Zhu S, Lu S, Dai Z, Jin Y (April 2000). "[An experimental study on cerulenin induced apoptosis of human colonic cancer cells]". Zhonghua Bing Li Xue Za Zhi (in Chinese). 29 (2): 115–8. PMID 11866903.
  7. ^ Ghosh MK, Amudha R, Jayachandran S, Sakthivel N (2002). "Detection and quantification of phytotoxic metabolites of Sarocladium oryzae in sheath rot-infected grains of rice". Lett. Appl. Microbiol. 34 (6): 398–401. doi:10.1046/j.1472-765X.2002.01111.x. PMID 12028418.

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