1. Retrorsine Hydrochloride
2. Retrorsine, (15e)-isomer
3. Usaramine
1. Beta-longilobine
2. 480-54-6
3. Retrorsin
4. Xj86xwl8iy
5. 12,18-dihydroxysenecionan-11,16-dione
6. Mls002153926
7. Chebi:8822
8. Cis-retronecic Acid Ester Of Retronecine
9. Ccris 4338
10. Hsdb 3530
11. Unii-xj86xwl8iy
12. Nsc 107659
13. Retrorcine
14. 12,18-dihydroxy-senecionan-11,16-dione
15. Senecionan-11,16-dione, 12,18-dihydroxy-
16. Nsc-107659
17. Prestwick_562
18. Retrorsin, Hplc Grade
19. Retrorsine [mi]
20. Prestwick2_000637
21. Prestwick3_000637
22. Retrorsine [hsdb]
23. Retrorsine [iarc]
24. Trans-15-ethylidene-12beta-hydroxy-12alpha-hydroxymethyl-13beta-methylsenec-1-enine
25. (15z)-12,18-dihydroxysenecionan-11,16-dione
26. Bspbio_000634
27. 3-ethylidene-3,4,5,6,9,11,13,14,14a,14b-decahydro-6-hydroxy-6-hydroxymethyl-5-methyl(1,6)dioxacyclododeca(2,3,4-gh)pyrrolizidine-2,7-dione
28. Schembl133058
29. Bpbio1_000698
30. Chembl496894
31. Dtxsid6021242
32. Retrorsine, >=90% (hplc)
33. Hms1545m22
34. Hms1569p16
35. Hms2096p16
36. Hms2231j18
37. Hy-n6638
38. Mfcd00870195
39. Zinc96551165
40. Akos024282552
41. Ccg-208491
42. Ncgc00142486-03
43. Smr001233270
44. Cs-0062871
45. Sr-01000841220
46. Sr-01000841220-3
47. Brd-k42142750-001-01-5
48. Brd-k42142750-001-04-9
49. Q27108154
50. (z)-ethylidene-hydroxy-(hydroxymethyl)-methyl-[?]dione
51. (1,6)dioxacyclododecino(2,3,4-gh)pyrrolizine-2,7-dione, 3-ethylidene-3,4,5,6,9,11,13,14,14a,14b-decahydro-6-hydroxy-6-(hydroxymethyl)-5-methyl-, (3z,5r,6s,14ar,14br)-
52. (1r,4z,6r,7s,17r)-4-ethylidene-7-hydroxy-7-(hydroxymethyl)-6-methyl-2,9-dioxa-14-azatricyclo[9.5.1.0??,??]heptadec-11-ene-3,8-dione
53. (5r,6s,9a1r,14ar,z)-3-ethylidene-6-hydroxy-6-(hydroxymethyl)-5-methyl-3,4,5,6,9,9a1,11,13,14,14a-decahydro-[1,6]dioxacyclododecino[2,3,4-gh]pyrrolizine-2,7-dione
| Molecular Weight | 351.4 g/mol |
|---|---|
| Molecular Formula | C18H25NO6 |
| XLogP3 | 0.6 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 7 |
| Rotatable Bond Count | 1 |
| Exact Mass | 351.16818752 g/mol |
| Monoisotopic Mass | 351.16818752 g/mol |
| Topological Polar Surface Area | 96.3 Ų |
| Heavy Atom Count | 25 |
| Formal Charge | 0 |
| Complexity | 627 |
| Isotope Atom Count | 0 |
| Defined Atom Stereocenter Count | 4 |
| Undefined Atom Stereocenter Count | 0 |
| Defined Bond Stereocenter Count | 1 |
| Undefined Bond Stereocenter Count | 0 |
| Covalently Bonded Unit Count | 1 |
Antineoplastic Agents, Phytogenic
Agents obtained from higher plants that have demonstrable cytostatic or antineoplastic activity. (See all compounds classified as Antineoplastic Agents, Phytogenic.)
In animal studies highest concentrations were found in the liver, lungs, kidneys and spleen. /pyrrolizidine alkaloids/
IPCS; Poisons Information Monograph (484) on Senecio Vulgaris L. (September 1989). Available from, as of September 15, 2003: https://www.inchem.org/documents/pims/plant/senecio.htm
When pyrrolizidine alkaloids, retrorsine 60 mg/kg, retrorsine n-oxide 60 mg/kg were administered ip to rats, 0.2-12.4% of the doses were excreted in the urine within 24 hr as metabolic pyrroles. There was a rough correlation between the hepatotoxicity of alkaloids and the amount of pyrroles to which they gave rise to in vivo. When rats were dosed orally or ip with retrorsine 50 mg/kg and sacrificed after various times, metabolic pyrroles were found bound strongly to the liver, and to /lesser/ extent the lung and other organs, for 48 hr or more after being formed.
MATTOCKS AR; TOXICITY OF PYRROLIZIDINE ALKALOIDS; NATURE (LONDON) 217(5130) 723 (1968)
Studies with retrorsine have confirmed the formation of the n-oxide and pyrrolic metabolites /retrorsine pyrrole/ by the mixed-function oxidase system of the microsomal fraction of rat liver.
IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: https://monographs.iarc.fr/ENG/Classification/index.php, p. V10 307 (1976)
In animals, the major metabolic routes of pyrrolizidine alkaloids are: (a) hydrolysis of the ester groups; (b) N-oxidation; and (c) dehydrogenation of the pyrrolizidine nucleus to pyrrolic derivatives. Routes (a) and (b) are believed to be detoxification mechanisms. Route (c) leads to toxic metabolites. Route (a) occurs in liver and blood; routes (b) and (c) are brought about in the liver by the microsomal mixed function oxidase system. /pyrrolizidine alkaloids/
IPCS; Poisons Information Monograph (484) on Senecio Vulgaris L. (September 1989). Available from, as of September 15, 2003: https://www.inchem.org/documents/pims/plant/senecio.htm
The in vivo metabolism and excretion of the urinary metabolites from the pyrrolizidine alkaloids (PAs), retrorsine (RET) and retrorsine-N-oxide (RET-NO) have been studied in rats. Isatinecic acid (INA), pyrrolic metabolites, N-oxides and retronecine accounted for 31.0, 10.3, 10.8 and 0.39% of the administered RET. Predosing rats with triorthocresyl phosphate (TOCP), had no effect on the excretion of pyrrolic metabolites and INA. Phenobarbital (PB) increased the excretion of both pyrrolic metabolites and INA with a corresponding decrease in the excretion of RET and N-oxides; the retronecin levels remained unaltered. When RET-NO was administered i.p., the urinary levels of pyrrolic metabolites, INA and RET were decreased relative to those treated with RET. The p.o. administration of RET-NO produced significantly higher levels of pyrrolic metabolites, INA and RET. These results suggest that esterase hydrolysis plays a minor role in the formation of INA and that a common metabolic pathway may exist between pyrrolic metabolites and INA formation.
PMID:8452478 Chu P et al; Arch Toxicol 67 (1): 39-43 (1993)
...Retrorsine was administered to a cohort of young adult male rats and examined induction or enhanced expression of mRNA and protein for widely studied hepatic CYP isoforms spanning four families together with the essential enzyme CYP reductase. The protein levels of normally expressed CYPs 1A2, 2B1/2, and 2E1 increase significantly in rat liver microsomes from retrorsine-treated rats compared to untreated control rats (P< 0.05), but protein levels of CYP 4A3, CYP 3A1, and CYP reductase were unchanged after retrorsine treatment. In addition, CYP 1A1 mRNA and protein, which are not detectable in the livers of control rats, were induced after retrorsine exposure. The results of the present study demonstrate enhanced or induced expression of hepatic CYPs 1A1, 1A2, 2E1, and 2B1/2 in response to retrorsine exposure in rats, suggesting that one or more of these enzymes may be involved in retrorsine metabolism.
PMID:10891289 Gordon G et al; Exp Mol Pathol 69 (1): 17-26 (2000)
For more Metabolism/Metabolites (Complete) data for RETRORSINE (6 total), please visit the HSDB record page.
Within a few hours, only a relatively small proportion of the administered dose remains in the body. Much of this is in the form of metabolites bound to tissue contents. A pyrrolizidine N-oxide disappeared from the serum after IV administration in animals, with initial half-lives of 3 -20 minutes. /pyrrolizidine alkaloids/
IPCS; Poisons Information Monograph (484) on Senecio Vulgaris L. (September 1989). Available from, as of September 15, 2003: https://www.inchem.org/documents/pims/plant/senecio.htm
The dehydropyrrolizine metabolites...react with water, DNA, and other cell components in vitro, and are cytotoxic. The bioactivation is mediated by a c-oxygenation, a reaction which proceeds very slowly in microsomes from neonates but which increases rapidly in microsomes obtained up to 5 days after birth.
The Chemical Society. Foreign Compound Metabolism in Mammals Volume 3. London: The Chemical Society, 1975., p. 473
Intragastric admin of 7 mg/kg retrorsine inhibited incorporation of labeled amino acids into rat liver and plasma proteins in vivo. The toxin affected the liver ribosomal aggregates, causing increases in proportion of monomers plus dimers. Incorporation of orotate into liver nuclear RNA was inhibited 1 hr after admin.
VILLA-TREVINO S, LEAVER DD; EFFECTS OF THE HEPATOTOXIC AGENTS RETRORSINE AND AFLATOXIN B1 ON HEPATIC PROTEIN SYNTHESIS IN THE RAT; BIOCHEM J 109(1) 87 (1968)
Two procedures were used to study the role of liver glutathione in acute toxicity of retrorsine in rats. Glutathione levels in rats were increased to about double that of controls by cysteine and to about 25% that of control by 2-chloroethanol. Acute LD50 of retrorsine (42 mg/kg) to rats is increased by pretreatment with cysteine to 83 mg/kg and decreased by pretreatment with 2-chloroethanol to 23 mg/kg. Two hr after admin of retrorsine (60 mg/kg) the levels of pyrrolic metabolites in the livers of animals pretreated with cysteine or c-chloroethanol are, respectively, about 60% and 200% those of rats given no pretreatment. By 24 hr, the glutathione concentration in livers of retrorsine-dosed rats is higher than those of corresponding controls. Treatment of rats with retrorsine (60 mg/kg) causes a fall in liver concentration of cytochrome p-450, 24 hr after dosing. This loss of cytochrome p-450 is increased in rats pretreated with chloroethanol.
WHITE I NH; THE ROLE OF LIVER GLUTATHIONE IN THE ACUTE TOXICITY OF RETRORSINE TO RATS; CHEM-BIOL INTERACT 13(3-4) 333 (1976)
The activation of the alkaloids by mixed-function oxidases leads to pyrrolic dehydro-alkaloids which are reactive alkylating agents. The liver necrosis results from binding of the metabolites with the liver cell. Some metabolites are released into the circulation and are believed to pass beyond the liver to the lung causing vascular lesions. The pyrrolic metabolites are cytotoxic and act on the hepatocytes and on the endothelium of blood vessels of the liver and lung. /pyrrolizidine alkaloids/
IPCS; Poisons Information Monograph (484) on Senecio Vulgaris L. (September 1989). Available from, as of September 15, 2003: https://www.inchem.org/documents/pims/plant/senecio.htm
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