 | |
| Names | |
|---|---|
| IUPAC name 3β-Hydroxy-14,15β-epoxy-5β-bufa-20,22-dienolid-16β-yl acetate | |
| Systematic IUPAC name (1R,2R,2aR,3aS,3bR,5aR,7S,9aS,9bS,11aR)-7-Hydroxy-9a,11a-dimethyl-1-(2-oxo-2H-pyran-5-yl)hexadecahydronaphtho[1′,2′:6,7]indeno[1,7a-b]oxiran-2-yl acetate | |
| Other names Cinobufagin | |
| Identifiers | |
| |
3D model (JSmol) | |
| ChEBI | |
| ChEMBL | |
| ChemSpider |
|
| ECHA InfoCard | 100.164.680 |
| EC Number |
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| KEGG | |
| UNII | |
| |
| |
| Properties | |
| C26H34O6 | |
| Molar mass | 442.552 g·mol−1 |
| Hazards | |
| Occupational safety and health (OHS/OSH): | |
Main hazards | Toxic |
| GHS labelling: | |
 | |
| Danger | |
| H300,H310,H330 | |
| P260,P262,P264,P270,P271,P280,P284,P301+P310,P302+P350,P304+P340,P310,P320,P321,P322,P330,P361,P363,P403+P233,P405,P501 | |
Except where otherwise noted, data are given for materials in theirstandard state (at 25 °C [77 °F], 100 kPa). | |
Cinobufagin is acardiotoxicbufanolidesteroid secreted by the AsiatictoadBufo gargarizans. It has similar effects todigitalis and is used intraditional Chinese medicine.[1]
Cinobufagin, as well as other bufadienolides, can be isolated from the traditional Chinese medicine called ChanSu. ChanSu is made from a multitude of chemicals present inBufo gargarizans secretions. Resibufogenin can be eluted out with silica gel columnchromatography, using a 5:1 ratio ofcyclohexane toacetone for thesolvent in the mobile phase. Subsequently, cinobufagin and bufalin can be separated and purified using anHPLC column with a 72:28methanol towater solvent. Yang et al. confirmed this method of isolation for cinobufagin withProton NMR.[2]
Cinobufagin has been shown to have clinical applications incancer treatment as well as immunomodulatory andanalgesic properties.[citation needed]
In human adrenocortical cells, cinobufagin inhibits the secretion of aldosterone and cortisol. Cinobufagin is able to inhibit the expression of the StAR protein as well as bind the transcription factor SF-1, which normally binds to the promoter for the StAR gene. This results in less StARprotein product and decreased levels ofaldosterone andcortisol synthesis. Cinobufagin first binds to a Ca2+/K+ plasma membraneATPase, subsequently inducing the phosphorylation ofextracellular signal-regulated kinases (ERK). Phosphorylated ERK then blocks the SF-1transcription factor from binding to thepromoter region of the StARgene.
Thus, cinobufagin plays important roles in regulation ofsteroid synthesis andgene expression. It is speculated that cinobufagin may have therapeutic roles in treatment ofCushing's syndrome andheart failure.[3]
In vitro, cinobufagin can stimulate the proliferation of immune cells including splenocytes,peritonealmacrophages,T helper cells andcytotoxic T cells. Additionally cinobufagin can modulate levels ofcytokines produced by immune cells. Exposure to cinobufagin increases levels ofinterferon gamma andtumor necrosis factor alpha while decreasing overall levels ofinterleukin 4 andinterleukin 10.[4]
Cinobufagin has been shown to increase pain threshold levels in mice to thermal and mechanical stimuli. It is thought to trigger increased synthesis of β-END and the up-regulation of themu opioid receptor in mouse tumor tissue thereby leading to pain relief. β-END binds themu opioid receptor to cause theanalgesic effect.[5]
C. elegans can catabolize cinobufagin into five distinct metabolites, each of which has been shown to have cytotoxic effects toHeLa cancer cells.[6]
Cinobufagin can inducecell cycle arrest at the G2 and M phases as well as induceapoptosis inosteosarcoma cells. Potentially, cinobufagin could be used to stop proliferation of osteosarcoma cells as well as to induceapoptosis them. At the protein level, cinobufagin treated osteosarcoma cells showed an increase in the Bax and cleaved-PARP apoptotic proteins, while inhibiting theGSK-3β/NF-κB signaling pathway.[7]
With regards to the induction ofapoptosis, cinobufagin has been shown to selectively bind K+/Na+ATPases incaninekidney cells to trigger a signaling cascade which leads tocaspase dependent pathways forapoptosis. It is through the activation ofcaspases that Cinobufagin can causeapoptosis.[8]
