Integerrimine

• CAT Number: I029389
• CAS Number: 480-79-5
• Molecular Formula: C18H25NO5
• Molecular Weight: 335.4
• Purity: 98%
• Synonyms: Integerrimine; Senecionine; Squalidin; Squalidine
• Target: Disease Research Fields
• Solubility: Soluble in DMSO
• Appearance: Solid powder
• Storage: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
• IUPAC Name: (15Z)-12-hydroxysenecionan-11,16-dione
• InChI: InChI=1S/C18H25NO5/c1-4-12-9-11(2)18(3,22)17(21)23-10-13-5-7-19-8-6-14(15(13)19)24-16(12)20/h4-5,11,14-15,22H,6-10H2,1-3H3/b12-4-/t11-,14-,15-,18-/m1/s1
• InChIKey: HKODIGSRFALUTA-JTLQZVBZSA-N
• SMILES: [H][C@@]12[C@]([H])(OC(/C(C[C@H]([C@]3(O)C)C)=CC)=O)CCN1CC=C2COC3=O

Integerrimine (Cat.No:I029389) is a natural pyrrolizidine alkaloid, possessing significant hepatotoxicity to humans and animals after metabolic activation by liver P450 enzymes.

Reference

1: Muluneh F, Häkkinen MR, El-Dairi R, Pasanen M, Juvonen RO. A New Glutathione Conjugate of the Pyrrolizidine Alkaloids Produced by Human Cytosolic Enzyme Dependent Reactions in vitro. Rapid Commun Mass Spectrom. 2018 May 22. doi: 10.1002/rcm.8173. [Epub ahead of print] PubMed PMID: 29788543.
2: Housecroft CE. Tolerating Toxins: Grasshoppers that Feast on Pyrrolizidine Alkaloids §. Chimia (Aarau). 2018 Mar 30;72(3):156-157. doi: 10.2533/chimia.2018.156. PubMed PMID: 29631671.
3: Waizenegger J, Braeuning A, Templin M, Lampen A, Hessel-Pras S. Structure-dependent induction of apoptosis by hepatotoxic pyrrolizidine alkaloids in the human hepatoma cell line HepaRG: Single versus repeated exposure. Food Chem Toxicol. 2018 Apr;114:215-226. doi: 10.1016/j.fct.2018.02.036. Epub 2018 Feb 16. PubMed PMID: 29458164.
4: Gottschalk C, Ostertag J, Meyer K, Gehring K, Thyssen S, Gareis M. Influence of grass pellet production on pyrrolizidine alkaloids occurring in Senecio aquaticus-infested grassland. Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 2018 Apr;35(4):750-759. doi: 10.1080/19440049.2018.1430901. Epub 2018 Feb 23. PubMed PMID: 29377789.
5: Cheng D, Nguyen VT, Ndihokubwayo N, Ge J, Mulder PPJ. Pyrrolizidine alkaloid variation in Senecio vulgaris populations from native and invasive ranges. PeerJ. 2017 Aug 14;5:e3686. doi: 10.7717/peerj.3686. eCollection 2017. PubMed PMID: 28828276; PubMed Central PMCID: PMC5560238.
6: Cheng X, Liao M, Diao X, Sun Y, Zhang L. Screening and identification of metabolites of two kinds of main active ingredients and hepatotoxic pyrrolizidine alkaloids in rat after lavage Farfarae Flos extract by UHPLC-Q-TOF-MS mass spectrometry. Biomed Chromatogr. 2018 Feb;32(2). doi: 10.1002/bmc.4047. Epub 2017 Aug 18. PubMed PMID: 28702943.
7: Liu W, Li X, Zhou B, Fang S, Ho W, Chen H, Liang H, Ye L, Tang J. Differential induction of apoptosis and autophagy by pyrrolizidine alkaloid clivorine in human hepatoma Huh-7.5 cells and its toxic implication. PLoS One. 2017 Jun 26;12(6):e0179379. doi: 10.1371/journal.pone.0179379. eCollection 2017. PubMed PMID: 28650983; PubMed Central PMCID: PMC5484491.
8: Yang M, Ruan J, Gao H, Li N, Ma J, Xue J, Ye Y, Fu PP, Wang J, Lin G. First evidence of pyrrolizidine alkaloid N-oxide-induced hepatic sinusoidal obstruction syndrome in humans. Arch Toxicol. 2017 Dec;91(12):3913-3925. doi: 10.1007/s00204-017-2013-y. Epub 2017 Jun 15. PubMed PMID: 28620673.
9: Martinello M, Borin A, Stella R, Bovo D, Biancotto G, Gallina A, Mutinelli F. Development and validation of a QuEChERS method coupled to liquid chromatography and high resolution mass spectrometry to determine pyrrolizidine and tropane alkaloids in honey. Food Chem. 2017 Nov 1;234:295-302. doi: 10.1016/j.foodchem.2017.04.186. Epub 2017 May 2. PubMed PMID: 28551239.
10: Preliasco M, Gardner D, Moraes J, González AC, Uriarte G, Rivero R. Senecio grisebachii Baker: Pyrrolizidine alkaloids and experimental poisoning in calves. Toxicon. 2017 Jul;133:68-73. doi: 10.1016/j.toxicon.2017.05.004. Epub 2017 May 3. PubMed PMID: 28478055.
11: Zhang W, Huai W, Zhang Y, Shen J, Tang X, Xie X, Wang K, Fan H. Ultra-Performance Liquid Chromatography Hyphenated with Quadrupole-Orbitrap Mass Spectrometry for Simultaneous Determination of Necine-Core-Structure Pyrrolizidine Alkaloids in Crotalaria sessiliflora L. without all Corresponding Standards. Phytochem Anal. 2017 Sep;28(5):365-373. doi: 10.1002/pca.2683. Epub 2017 Mar 23. PubMed PMID: 28332747.
12: Yang X, Wang H, Ni HM, Xiong A, Wang Z, Sesaki H, Ding WX, Yang L. Inhibition of Drp1 protects against senecionine-induced mitochondria-mediated apoptosis in primary hepatocytes and in mice. Redox Biol. 2017 Aug;12:264-273. doi: 10.1016/j.redox.2017.02.020. Epub 2017 Mar 2. PubMed PMID: 28282614; PubMed Central PMCID: PMC5344326.
13: Liu X, Klinkhamer PGL, Vrieling K. The effect of structurally related metabolites on insect herbivores: A case study on pyrrolizidine alkaloids and western flower thrips. Phytochemistry. 2017 Jun;138:93-103. doi: 10.1016/j.phytochem.2017.02.027. Epub 2017 Mar 6. PubMed PMID: 28267991.
14: Cao K, Xu Y, Mu X, Zhang Q, Wang R, Lv J. Sensitive determination of pyrrolizidine alkaloids in Tussilago farfara L. by field-amplified, sample-stacking, sweeping micellar electrokinetic chromatography. J Sep Sci. 2016 Nov;39(21):4243-4250. doi: 10.1002/jssc.201600762. PubMed PMID: 27673325.
15: Mollinedo P, Vila JL, Arando H, Sauvain M, Deharo E, Bravo JA. Anti-infective assessment of Senecio smithioides (Asteraceae) and isolation of 9-oxoeuryopsin, a furanoeremophilane-type sesquiterpene with antiplasmodial activity. Nat Prod Res. 2015 Nov 25:1-4. [Epub ahead of print] PubMed PMID: 26606687.
16: Martins CH, Cunha BP, Solferini VN, Trigo JR. Feeding on Host Plants with Different Concentrations and Structures of Pyrrolizidine Alkaloids Impacts the Chemical-Defense Effectiveness of a Specialist Herbivore. PLoS One. 2015 Oct 30;10(10):e0141480. doi: 10.1371/journal.pone.0141480. eCollection 2015. PubMed PMID: 26517873; PubMed Central PMCID: PMC4627748.
17: Mudge EM, Jones AM, Brown PN. Quantification of pyrrolizidine alkaloids in North American plants and honey by LC-MS: single laboratory validation. Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 2015;32(12):2068-74. doi: 10.1080/19440049.2015.1099743. Epub 2015 Oct 20. PubMed PMID: 26482059.
18: Sandini TM, Udo MS, Reis-Silva TM, Sanches D, Bernardi MM, Flório JC, Spinosa Hde S. Prenatal exposure to integerrimine N-oxide enriched butanolic residue from Senecio brasiliensis affects behavior and striatal neurotransmitter levels of rats in adulthood. Int J Dev Neurosci. 2015 Dec;47(Pt B):157-64. doi: 10.1016/j.ijdevneu.2015.09.003. Epub 2015 Sep 28. PubMed PMID: 26416213.
19: Chizzola R. Pyrrolizidine Alkaloids in Adenostyles alliariae and A. glabra from the Austrian Alps. Nat Prod Commun. 2015 Jul;10(7):1179-80. PubMed PMID: 26411004.
20: Chen P, Wang Y, Chen L, Jiang W, Niu Y, Shao Q, Gao L, Zhao Q, Yan L, Wang S. Comparison of the anti-inflammatory active constituents and hepatotoxic pyrrolizidine alkaloids in two Senecio plants and their preparations by LC-UV and LC-MS. J Pharm Biomed Anal. 2015 Nov 10;115:260-71. doi: 10.1016/j.jpba.2015.07.014. Epub 2015 Jul 26. PubMed PMID: 26257293.