Bufotaline

Names

[ CAS No. ]:
471-95-4

[ Name ]:
Bufotaline

[Synonym ]:
Bufotaline
Bufotalin std.
16-(Acetyloxy)-3,14-dihydroxybufa-20,22-dienolide
BUFOTALIN(SH)
BUFOTALIN SULFATE
Bufa-20,22-dienolide, 16-(acetyloxy)-3,14-dihydroxy-, (3β,5β,16β)-
(3b,5b,16b)-16-(Acetyloxy)-3,14-dihydroxybufa-20,22-dienolide
(3S,5R,8R,9S,10S,13R,14S,16S,17R)-3,14-dihydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-16-yl acetate
5β-Bufa-20,22-dienolide, 3β,14,16β-trihydroxy-, 16-acetate (8CI)
Bufotalin
3b,14,16b-Trihydroxy-5b-bufa-20,22-dienolide 16-Acetate
(3β,5β,16β)-16-Acetoxy-3,14-dihydroxybufa-20,22-dienolide

Biological Activity

[Description]:

Bufotalin is a cardiotoxic bufanolide steroid, cardiac glycoside analogue, secreted by a number of toad species; a novel anti-osteoblastoma agent.IC50 value:Target:in vitro: bufotalin induced osteoblastoma cell death and apoptosis in dose- and time-dependent manners. Further, bufotalin induced endoplasmic reticulum (ER) stress activation in osteoblastoma cells, the latter was detected by the induction of C/EBP homologous protein (CHOP), phosphorylation of inositol-requiring enzyme 1 (IRE1) and PKR-like endoplasmic reticulum kinase (PERK), as well as caspase-12 activation [1]. Bufotalin was the most potent active compound among these four bufadienolides, and it exerted stronger inhibitory effect on the viability of doxorubicin-induced multidrug resistant liver cancer cells (R-HepG2) than that of their parent cells HepG2. bufotalin treatment induced cell cycle arrest at G(2)/M phase through down-regulation of Aurora A, CDC25, CDK1, cyclin A and cyclin B1, as well as up-regulation of p53 and p21. Bufotalin treatment also induced apoptosis which was accompanied by decrease in mitochondrial membrane potential, increases in intracellular calcium level and reactive oxygen species production, activations of caspase-9 and -3, cleavage of poly ADP-ribose polymerase (PARP) as well as changes in the expressions of bcl-2 and bax [2]. Bufotalin promoted death receptor-mediated cell death, especially TRAIL-induced apoptosis, through activation of caspase-3 and PARP-1. Cotreatment of bufotalin with TRAIL resulted in the downregulation of anti-apoptotic proteins, including Bcl-XL, Mcl-1, survivin and XIAP, and the up-regulation of MAPKs and TRAIL receptor DR5. In addition, phosphorylation of STAT1 was strongly inhibited by bufotalin [3]. externalization of phosphatidylserine, accumulation of sub-G(1) cells, fragmentation of DNA, and formation of apoptotic bodies were observed in bufotalin-treated Hep 3B cells [4].

[Related Catalog]:

Signaling Pathways >> Others >> Others

Natural Products >> Steroids

Research Areas >> Cancer

[References]

[1]. Zhu YR, et al. Bufotalin-induced apoptosis in osteoblastoma cells is associated with endoplasmic reticulum stress activation. Biochem Biophys Res Commun. 2014 Aug 15;451(1):112-8.

[2]. Zhang DM, et al. Bufotalin from Venenum Bufonis inhibits growth of multidrug resistant HepG2 cells through G2/M cell cycle arrest and apoptosis. Eur J Pharmacol. 2012 Oct 5;692(1-3):19-28.

[3]. Waiwut P, et al. Bufotalin sensitizes death receptor-induced apoptosis via Bid- and STAT1-dependent pathways. Int J Oncol. 2012 Jan;40(1):203-8.

[4]. Su CL, et al. Involvement of caspases and apoptosis-inducing factor in bufotalin-induced apoptosis of Hep 3B cells. J Agric Food Chem. 2009 Jan 14;57(1):55-61.

[Related Small Molecules]

Chemical & Physical Properties

[ Density]:
1.3±0.1 g/cm3

[ Boiling Point ]:
591.7±50.0 °C at 760 mmHg

[ Melting Point ]:
223°C (rough estimate)

[ Molecular Formula ]:
C₂₆H₃₆O₆

[ Molecular Weight ]:
444.560

[ Flash Point ]:
195.8±23.6 °C

[ Exact Mass ]:
444.251190

[ PSA ]:
96.97000

[ LogP ]:
2.54

[ Vapour Pressure ]:
0.0±3.8 mmHg at 25°C

[ Index of Refraction ]:
1.587

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: EI3150000

CHEMICAL NAME :: 5-beta-Bufa-20,22-dienolide, 3-beta,14,16-beta-trihydroxy-, 16-acetate

CAS REGISTRY NUMBER :: 471-95-4

LAST UPDATED :: 199109

DATA ITEMS CITED :: 8

MOLECULAR FORMULA :: C26-H36-O6

MOLECULAR WEIGHT :: 444.62

WISWESSER LINE NOTATION :: L E5 B666TJ A1 E1 GOV1 IQ OQ F- ET6OVJ

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 400 ug/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: CTOXAO Clinical Toxicology. (New York, NY) V.1-18, 1968-81. For publisher information, see JTCTDW. Volume(issue)/page/year: 4,331,1971

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 4130 ug/kg

TOXIC EFFECTS :: Behavioral - tremor Behavioral - convulsions or effect on seizure threshold Behavioral - antipsychotic

REFERENCE :: CPBTAL Chemical and Pharmaceutical Bulletin. (Japan Pub. Trading Co., USA, 1255 Howard St., San Francisco, CA 94103) V.6- 1958- Volume(issue)/page/year: 24,1714,1976

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Unreported

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 1131 ug/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: PHUZBI Pharmazie in Unserer Zeit. (VCH Pub., Inc., 303 N.W. 12th Ave., Deerfield Beach, FL 33441) V.1- 1972- Volume(issue)/page/year: 13,129,1984

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 980 ug/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: CRSBAW Comptes Rendus des Seances de la Societe de Biologie et de Ses Filiales. (SPPIF, B.P.22, F-41353 Vineuil, France) V.1- 1849- Volume(issue)/page/year: 152,571,1958

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 360 ug/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: CRSBAW Comptes Rendus des Seances de la Societe de Biologie et de Ses Filiales. (SPPIF, B.P.22, F-41353 Vineuil, France) V.1- 1849- Volume(issue)/page/year: 152,571,1958

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Mammal - cat

DOSE/DURATION :: 136 ug/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: JPETAB Journal of Pharmacology and Experimental Therapeutics. (Williams & Wilkins Co., 428 E. Preston St., Baltimore, MD 21202) V.1- 1909/10- Volume(issue)/page/year: 74,223,1942

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Unreported

SPECIES OBSERVED :: Mammal - cat

DOSE/DURATION :: 130 ug/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: PHUZBI Pharmazie in Unserer Zeit. (VCH Pub., Inc., 303 N.W. 12th Ave., Deerfield Beach, FL 33441) V.1- 1972- Volume(issue)/page/year: 13,129,1984

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Unreported

SPECIES OBSERVED :: Amphibian - frog

DOSE/DURATION :: 1200 ug/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: AEXPBL Archiv fuer Experimentelle Pathologie und Pharmakologie. (Leipzig, Ger. Dem. Rep.) V.1-109, 1873-1925. For publisher information, see NSAPCC. Volume(issue)/page/year: 86,138,1920

Safety Information

[ RIDADR ]:
UN 3172

[ Packaging Group ]:
II

[ Hazard Class ]:
6.1(a)

[ HS Code ]:
29329990