Annonacin

Annonacin

IUPAC name (5S)-5-Methyl-3-[(2R,8R,13R)-2,8,13-trihydroxy-13- [(2R,5R)-5-[(1R)-1- hydroxytridecyl]-2-tetrahydrofuranyl] tridecyl]-5H-furan-2-one
Identifiers
CAS number	111035-65-5^Y
PubChem	354398
ChemSpider	314587^Y
Jmol-3D images	Image 1 Image 2
SMILES CCCCCCCCCCCCC(C1CCC(O1)C(CCCCC(CCCCCC(CC2=CC(OC2=O)C)O)O)O)O O=C\1O[C@H](/C=C/1C[C@H](O)CCCCC[C@@H](O)CCCC[C@@H](O)[C@@H]2O[C@@H]([C@H](O)CCCCCCCCCCCC)CC2)C
InChI InChI=1S/C35H64O7/c1-3-4-5-6-7-8-9-10-11-15-21-31(38)33-23-24-34(42-33)32(39)22-17-16-19-29(36)18-13-12-14-20-30(37)26-28-25-27(2)41-35(28)40/h25,27,29-34,36-39H,3-24,26H2,1-2H3/t27-,29+,30+,31+,32+,33+,34+/m0/s1^Y Key: XNODZYPOIPVPRF-CGWDHHCXSA-N^Y InChI=1/C35H64O7/c1-3-4-5-6-7-8-9-10-11-15-21-31(38)33-23-24-34(42-33)32(39)22-17-16-19-29(36)18-13-12-14-20-30(37)26-28-25-27(2)41-35(28)40/h25,27,29-34,36-39H,3-24,26H2,1-2H3/t27-,29+,30+,31+,32+,33+,34+/m0/s1 Key: XNODZYPOIPVPRF-CGWDHHCXBQ
Properties
Molecular formula	C₃₅H₆₄O₇
Molar mass	596.88 g/mol
Y (verify) (what is: Y/N?) Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

Annonacin is a chemical found in some fruits such as the guanabana (and other from Annonaceae family). It is a member of the class of compounds known as acetogenins. Recent reports have shown that daily consumption in rats (3.8 and 7.6 mg per kg per day for 28 days) caused brain lesions consistent with Parkinson's disease.^[1] ^[2]

Along with other acetogenins, annonacin is reported to block mitochondrial complex I (NADH-dehydrogenase), which is responsible for the conversion of NADH to NAD⁺ and the build-up of a proton gradient over the mitochondrial inner membrane. This effectively disables a cell's ability to generate ATP via an oxidative pathway, ultimately forcing a cell into apoptosis or necrosis. ^[3]

References

^ Lannuzel, A; et al. (6 October 2003). "The mitochondrial complex i inhibitor annonacin is toxic to mesencephalic dopaminergic neurons by impairment of energy metabolism". Neuroscience (International Brain Research Organization) 121 (2): 287–296. doi:10.1016/S0306-4522(03)00441-X. PMID 14521988.
^ Champy, Pierre; Hoeglinger, Guenter U.; Feger, Jean; Gleye, Christophe; Hocquemiller, Reynald; Laurens, Alain; Guerineau, Vincent; Laprevote, Olivier; Medja, Fadia; Lombes, Anne; Michel, Patrick P.; Lannuzel, Annie; Hirsch, Etienne C.; Ruberg, Merle (2004). "Annonacin, a lipophilic inhibitor of mitochondrial complex I, induces nigral and striatal neurodegeneration in rats: Possible relevance for atypical parkinsonism in Guadeloupe". Journal of Neurochemistry 88 (1): 63–69. doi:10.1046/j.1471-4159.2003.02138.x. PMID 14675150.
^ McLaughlin, J.L. Paw paw and cancer: Annonaceous acetogenins from discovery to commercial products. J. Nat. Prod. 2008, 71, 1311-1321 and references cited