1. Monocrotaline Hydrochloride (13alpha,14alpha)-isomer
2. Monocrotaline, (all-xi)-isomer
1. 315-22-0
2. Crotaline
3. Monocrotalin
4. (-)-monocrotaline
5. Chebi:6980
6. Retronecine Cyclic 2,3-dihydroxy-2,3,4-trimethylglutarate
7. (13-alpha,14-alpha)-14,19-dihydro-12,13-dihydroxy-20-norcrotalanan-11,15-dione
8. Nci-c56462
9. 14,19-dihydro-12,13-dihydroxy-20-norcrotolanan-11,15-dione
10. 73077k8hyv
11. Nsc 28693
12. (3r,4r,5r,13ar,13br)-4,5-dihydroxy-3,4,5-trimethyl-4,5,8,10,12,13,13a,13b-octahydro-2h-[1,6]dioxacycloundecino[2,3,4-gh]pyrrolizine-2,6(3h)-dione
13. Ncgc00164256-01
14. Dsstox_cid_902
15. A 6080
16. Dsstox_rid_75856
17. Dsstox_gsid_20902
18. 2h-(1,6)dioxacycloundecino(2,3,4-gh)pyrrolizine-2,6(3h)-dione, 4,5,8,10,12,13,13a,13b-octahydro-4,5-dihydroxy-3,4,5-trimethyl-, (3r,4r,5r,13ar,13br)-
19. 2h-[1,6]dioxacycloundecino[2,3,4-gh]pyrrolizine-2,6(3h)-dione, 4,5,8,10,12,13,13a,13b-octahydro-4,5-dihydroxy-3,4,5-trimethyl-, (3r,4r,5r,13ar,13br)-
20. Ccris 416
21. Hsdb 3513
22. Sr-01000838886
23. (2,3,4-gh)pyrrolizine-2,6(3h)-dione, (4,5,8,10,12,13,13a,13b)-octahydro-4,5-dihydroxy-3,4,5-trimethyl-2h-(1,6)dioxacycloundecino-
24. Brn 0048732
25. Unii-73077k8hyv
26. Nsc-28693
27. Cas-315-22-0
28. Prestwick_338
29. 20-norcrotalanan-11,15-dione, 14,19-dihydro-12,13-dihydroxy-, (13alpha,14alpha)-
30. Spectrum_001224
31. Prestwick0_000603
32. Prestwick1_000603
33. Prestwick2_000603
34. Prestwick3_000603
35. Spectrum2_000906
36. Spectrum3_000947
37. Spectrum4_001057
38. Spectrum5_001233
39. Monocrotaline [mi]
40. 12-beta,13-beta-dihydroxy-12-alpha,13-alpha,14-alpha-trimethylcrotal-1-enine
41. 14,19-dihydro-12,13-dihydroxy(13-alpha,14-alpha)-20-norcrotalanan-11,15-dione
42. Monocrotaline [hsdb]
43. Monocrotaline [iarc]
44. Bspbio_000506
45. Kbiogr_001354
46. Kbioss_001704
47. 4-27-00-06660 (beilstein Handbook Reference)
48. Mls002153902
49. Divk1c_000959
50. Schembl164486
51. Spectrum1502252
52. Spbio_000752
53. Spbio_002725
54. Bpbio1_000558
55. Chembl521035
56. Megxp0_001899
57. Dtxsid9020902
58. Acon0_000305
59. Acon1_000179
60. Hms502p21
61. Kbio1_000959
62. Kbio2_001704
63. Kbio2_004272
64. Kbio2_006840
65. Kbio3_002014
66. Monocrotaline, Analytical Standard
67. Ninds_000959
68. Hms1569j08
69. Hms1921p04
70. Hms2096j08
71. Hms2235j12
72. Hy-n0750
73. Tox21_112094
74. Tox21_201509
75. Tox21_302874
76. Bdbm50480309
77. Ccg-39621
78. Mfcd00084656
79. S3812
80. Zinc53195720
81. Akos015969712
82. Akos032962048
83. Tox21_112094_1
84. Cs-6164
85. Fs-5652
86. Sdccgmls-0066675.p001
87. 20-norcrotalanan-11,15-dione, 14,19-dihydro-12,13-dihydroxy-, (13-alpha,14-alpha)-
88. Idi1_000959
89. Ncgc00179538-01
90. Ncgc00179538-02
91. Ncgc00179538-03
92. Ncgc00256518-01
93. Ncgc00259060-01
94. Ncgc00262539-03
95. Ac-34918
96. Smr001233251
97. N1470
98. Jacs 72: 158 (1950)
99. Q-100395
100. Sr-01000838886-3
101. Sr-01000838886-4
102. Brd-k65508953-001-05-5
103. Brd-k65508953-001-08-9
104. Q27107379
105. (1r,4r,5r,6r,16r)-5,6-dihydroxy-4,5,6-trimethyl-2,8-dioxa-13-azatricyclo[8.5.1.0??,??]hexadec-10-ene-3,7-dione
106. (1r,4r,5r,6r,16r)-5,6-dihydroxy-4,5,6-trimethyl-2,8-dioxa-13-azatricyclo[8.5.1.013,16]hexadec-10-ene-3,7-dione
107. (3r,4r,5r,8a1r,13ar)-4,5-dihydroxy-3,4,5-trimethyl-4,5,8,8a1,10,12,13,13a-octahydro-2h-[1,6]dioxacycloundecino[2,3,4-gh]pyrrolizine-2,6(3h)-dione
108. 109525-74-8
109. 2h-(1,6)dioxacycloundecino(2,3,4-gh)pyrrolizine-2,6(3h)-dione, 4,5,8,10,12,13,13a,13b-octahydro-4,5-dihydroxy-3,4,5-trimethyl-, (3r-(3r*,4r*,5r*,13ar*,13br*))-
110. Rel-(3r,4r,5r,8a1r,13ar)-4,5-dihydroxy-3,4,5-trimethyl-4,5,8,8a1,10,12,13,13a-octahydro-2h-[1,6]dioxacycloundecino[2,3,4-gh]pyrrolizine-2,6(3h)-dione
| Molecular Weight | 325.36 g/mol |
|---|---|
| Molecular Formula | C16H23NO6 |
| XLogP3 | -0.7 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 7 |
| Rotatable Bond Count | 0 |
| Exact Mass | 325.15253745 g/mol |
| Monoisotopic Mass | 325.15253745 g/mol |
| Topological Polar Surface Area | 96.3 Ų |
| Heavy Atom Count | 23 |
| Formal Charge | 0 |
| Complexity | 575 |
| Isotope Atom Count | 0 |
| Defined Atom Stereocenter Count | 5 |
| Undefined Atom Stereocenter Count | 0 |
| Defined Bond Stereocenter Count | 0 |
| Undefined Bond Stereocenter Count | 0 |
| Covalently Bonded Unit Count | 1 |
/Exptl Ther/ Antitumor effects of 22 pyrrolizidine alkaloids and derivatives were studied in mice with adenocarcinomas 755, l-1210 leukemia or sarcoma 180, rats with im or sc walker 256 carcinomasarcoma and in kb carcinoma cell cultures; 1 compound each was also tested in mice with ascites ehrlich carcinoma and hamsters with plasmacytoma number 1. Significant activity against the solid tumors, by CCNSC standards (58% or more decrease in tumor size), was seen with monocrotaline (NSC-28693) in 3 of the above tumors and in p-1. Monocrotaline n-oxide was without significant activity in any of the systems tested.
CULVENOR CC; J PHARM SCI 57(7) 1112 (1968)
/Exptl Ther/ Monocrotaline from crotalaria sessiliflora has been shown to be effective against human skin cancer and cancer of uterine cervix.
YIN L; YAOXUETONGBAO 16 (11): 54 (1981)
After sc administration of monocrotaline /in rats/, 50-70% of the dose was found in urine as unchanged monocrotaline... monocrotaline (or metabolite) concentration were highest in the liver, kidney and stomach.
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 295 (1976)
The pyrrolizidine alkaloid monocrotaline has been shown to cause hepatic necrosis and pulmonary hypertension in the rat. To better understand the mechanism of action, tissue distribution and covalent binding studies were conducted at 4 and 24 hr following administration of (14)C monocrotaline (60 mg/kg, 200 microCi/kg, sc). For the 4 hr study, the levels of monocrotaline equivalents were 85, 74, 67, 36, and 8 nmol/g of tissue for RBC, liver, kidney, lung, and plasma, respectively, while the covalent binding levels were 125, 132, 39, 64, 44 pmol/mg of protein for tissues as listed above. The 24 hr tissue distribution levels were 49, 25, 9, 10, 2 nmol/g of tissue for RBC, liver, kidney, lung, and plasma, respectively, while covalent binding was 74, 28, and 55 pmol/mg of protein for liver, kidney, and lung, respectively. We also studied the kinetics of (14)C monocrotaline (60 mg/kg, 10 microCi/kg, iv), which demonstrated rapid elimination of radioactivity with approximately 90% recovery of the injected radioactivity in the urine and bile by 7 hr. The plasma levels of radioactivity dropped from 113 nmol/g of monocrotaline equivalents to 11 nmol/g at 7 hr while RBC levels decreased from 144 to only 81 nmol/g at the same time point. The apparent retention of monocrotaline equivalents in the RBC suggests that this organ may act as the carrier of metabolites from the liver to other organs including the lung and may play a role in the pulmonary toxicity.
PMID:1673386 Estep JE et al; Drug Metab Dispos Biol Fate Chem 19 (1): 135-9 (1991)
Studies with monocrotaline have confirmed the formation of pyrrolic metabolites by the mixed-function oxidase system of the microsomal fraction of rat liver. Dehydromonocrotaline (monocrotaline pyrrole) is highly cytotoxic, producing pulmonary, cardiac, vascular and hepatic lesions similar to those produced by the parent alkaloid. It is a highly reactive alkylating agent which, on formation within the cell, reacts immediately with cell constituents to give soluble or bound secondary metabolites or hydrolyzes to the dehydroaminoalcohol, dehydroretronecine.
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 295 (1976)
Using microsomes from livers of phenobarbital-pretreated male rats, all 13 alkaloids tested were metabolized to n-oxide and pyrrole formation. The 2 pathways appeared to be independent. Ratio of n-oxide to pyrrolic metabolites varied, depending on type of ester: it was highest for open diester alkaloids and lowest for 12-membered macrocyclic diesters and for monoesters. Monocrotaline was one of those tested.
PMID:6825198 MATTOCKS AR, BIRD I; CHEM-BIOL INTERACT 43 (2): 209 (1983)
The comparative metabolism of the pyrrolizidine alkaloid, (14)C monocrotaline, was studied using rat and guinea pig hepatic microsomes. ... Esterase hydrolysis accounted for 92% of the metabolism in the guinea pig; the rat displayed no esterase activity. This result may explain the guinea pig's resistance to pyrrolizidine alkaloid toxicity. Dehydropyrrole was found to be the major pyrrolic metabolite in the guinea pig, although colorimetric analysis indicated multiple pyrrolic moieties in the rat microsomal incubations.
PMID:1352221 Dueker SR et al; Drug Metab Dispos Biol Fate Chem 20 (2): 275-80 (1992)
This report demonstrates that an Ehrlich reagent positive metabolite of monocrotaline and senecionine is excreted in the urine of male rats as an N-acetylcysteine conjugate of (+/-)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine ... This finding suggests that reactive metabolites of pyrrolizidine alkaloids generated in the liver can survive the aqueous environment of the circulatory system as glutathione conjugates or mercapturic acids.
PMID:2123045 Estep JE et al; Toxicol Lett 54 (1): 61-9 (1990)
For more Metabolism/Metabolites (Complete) data for MONOCROTALINE (7 total), please visit the HSDB record page.
The toxicology of monocrotaline is complex, and the mechanisms by which it causes lung injury, pulmonary hypertension, and right heart enlargement have remained elusive. ... Monocrotaline is bioactivated by the liver to a reactive, electrophilic pyrrole that travels via the circulation to the lung, where injury results. When low, iv doses of monocrotaline pyrrole are given to rats, a delay of several days occurs before lung injury and pulmonary hypertension become apparent. Moderate depletion of blood platelets around the time of the onset of lung injury lessens the subsequent development of right ventricular enlargement, suggesting a reduction in the pulmonary hypertensive response to monocrotaline pyrrole. This observation prompted a study of the role of platelet-derived mediators in the cardiopulmonary response to monocrotaline pyrrole. A stable analog of thromboxane A2(TxA2) caused a greater increase in right ventricular pressure in monocrotaline pyrrole treated rats compared to controls, and lungs isolated from monocrotaline pyrrole treated rats produced more TxB2 than those of controls. However, administration of drugs that either inhibited thromboxane synthesis or antagonized the effects of thromboxane did not afford protection from monocrotaline pyrrole in vivo. Serotonin, another vasoactive mediator released by platelets, caused an exaggerated vasoconstrictor response in isolated lungs from rats treated with monocrotaline pyrrole. Moreover, removal and inactivation of circulating serotonin by the pulmonary vasculature was impaired by treatment of rats with monocrotaline pyrrole. However, administration of serotonin receptor antagonists did not attenuate the cardiopulmonary effects of monocrotaline pyrrole in vivo. These results suggest that neither TxA2 nor serotonin is the sole mediator of the pneumotoxicity due to monocrotaline pyrrole. Thus, the mechanism by which platelets are involved in the pathogenesis of the pneumotoxic response to monocrotaline pyrrole remains an unsolved puzzle.
PMID:3130680 Roth RA, Ganey PE; Toxicol Appl Pharmacol 93 (3): 463-71 (1988)
Monocrotaline propagates changes in the contractile response of arterial smooth muscle, changes in smooth muscle Na/K-ATPase activity, release of platelet factors, and decreased serotonin transport by vascular endothelial cells.
Klaassen, C.D. (ed). Casarett and Doull's Toxicology. The Basic Science of Poisons. 6th ed. New York, NY: McGraw-Hill, 2001., p. 529
Effect of ip administration of monocrotaline on activities of hepatic epoxide hydrolase, and arylhydrocarbon hydroxylase was investigated in young, male long-evans rats. Monocrotaline failed to stimulate epoxide hydrolase while diminishing the activity of glutathione s-transferase, aminopyrine demethylase and AHH. There was no effect in vitro on hepatic drug-metabolizing enzymes studied except for slight stimulation of epoxide hydrolase activity and small reduction of aminopyrine demethylase activity.
PMID:6775360 MIRANDA CL ET AL; RES COMMUN CHEM PATHOL PHARMACOL 29 (3): 573-87 (1980)
... An active metabolite of monocrotaline, dehydromonocrotaline (DHM), alkylates guanines at the N7 position of DNA with a preference for 5'-GG and 5'-GA sequences. In addition, it generates piperidine- and heat-resistant multiple DNA crosslinks, as confirmed by electrophoresis and electron microscopy. On the basis of these findings, we propose that DHM undergoes rapid polymerization to a structure which is able to crosslink several fragments of DNA.
PMID:9826770 Full text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC147994 Pereira T et al; Nucleic Acids Res 26 (23): 5441-7 (1998)
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