Bufotalin

Bufotalin

Names
IUPAC name ((3S,5R,10S,13R,14S,16S,17R)-3,14-Dihydroxy-10,13-dimethyl-17-(6-oxopyran-3-yl)-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-16-yl)acetate
Identifiers
CAS Number	471-95-4 Y
ChEMBL	ChEMBL463064 Y
ChemSpider	16735710 Y
Jmol 3D model	Interactive image
PubChem	10119
InChI InChI=1S/C26H36O6/c1-15(27)32-21-13-26(30)20-6-5-17-12-18(28)8-10-24(17,2)19(20)9-11-25(26,3)23(21)16-4-7-22(29)31-14-16/h4,7,14,17-21,23,28,30H,5-6,8-13H2,1-3H3/t17-,18+,19+,20-,21+,23+,24+,25-,26+/m1/s1 Y Key: VOZHMAYHYHEWBW-NVOOAVKYSA-N Y InChI=1/C26H36O6/c1-15(27)32-21-13-26(30)20-6-5-17-12-18(28)8-10-24(17,2)19(20)9-11-25(26,3)23(21)16-4-7-22(29)31-14-16/h4,7,14,17-21,23,28,30H,5-6,8-13H2,1-3H3/t17-,18+,19+,20-,21+,23+,24+,25-,26+/m1/s1 Key: VOZHMAYHYHEWBW-NVOOAVKYBX
SMILES CC(=O)O[C@H]1C[C@@]2(C3CC[C@@H]4C[C@H](CC[C@@]4(C3CC[C@@]2([C@H]1C5=COC(=O)C=C5)C)C)O)O
Properties
Chemical formula	C26H36O6
Molar mass	444.57 g·mol−1
Appearance	crystalline solid
Vapor pressure	{{{value}}}
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Y verify (what is YN ?)
Infobox references

Bufotalin is a cardiotoxic bufanolide steroid, cardiac glycoside analogue, secreted by a number of toad species. Bufotalin can be extracted from the skin parotoid glands of several types of toad.

Sources

Rhinella marina (Cane toad), Rhaebo guttatus (Smooth-sided toad), Bufo melanostictus (Asian toad), and Bufo bufo (common European toad) are sources of bufotalin.

Traditional medicine

Bufotalin is part of Ch'an Su, a traditional Chinese medicine used for cancer. It is also known as Venenum Bufonis or senso (Japanese).

Toxicity

Specifically, in cats the lethal median dose is 0.13 mg/kg. and in dogs is 0.36 mg/kg (intravenous).

Knowing this it is advisable to monitor those functions continuously using an EKG. As there is no antidote against bufotalin all occurring symptoms need to be treated separately or if possible in combination with others. To increase the clearance theoretically, due to the similarities with digitoxin, cholestyramine, a bile salt, might help. Recent animal studies have shown that taurine restores cardiac functions.

Symptomatic measures include lignocaine, atropine and phenytoin for cardiac toxicity and intravenous potassium compounds to correct hyperkalaemia from its effect on the Na⁺/K⁺ ATPase pump.

Pharmacology and mechanism of action

Bufotalin is found to inhibit myocardial Na⁺/K⁺ ATPase activity by that increasing myocardial contractile force. Furthermore bufotalin was not found to affect the heart-rate with those changes in myocardial Na⁺/K⁺ ATPase activity.

After a single intravenous injection, bufotalin gets quickly distributed and eliminated from the blood plasma with a half-time of 28.6 minutes and a MRT of 14.7 min. After 30 minutes after an administration of bufotalin, the concentrations within the brain and lungs are significantly higher than those in blood and other tissues. It also increases cancer cell's susceptibility to apoptosis via TNF-α signalling by the BH3 interacting domain death agonist and STAT proteins.

Bufotalin induces apoptosis in vitro in human hepatocellular carcinoma Hep 3B cells and might involve caspases and apoptosis inducing factor (AIF). The use of bufotalin as a cancer treating compound is still in the experimental phase. It also arrests cell cycle at G(2)/M, by up- and down- regulation of several enzymes.

Pharmacokinetics

The mechanism of the biotransformation of bufotalin is still unknown. Researches found, that bufotalin is biotransformed into at least 5 different compounds.

The five known biotransformation products of bufotalin.

Chemical properties

If bufotalin is esterified with suberyl arginine, the bufotalin-like steroid bufotoxin is obtained.