|Toxicon. 2016 Feb;110:27-34. |
|Bufadienolides from parotoid gland secretions of Cuban toad Peltophryne fustiger (Bufonidae): Inhibition of human kidney Na(+)/K(+)-ATPase activity.[Pubmed: 26615828 ]|
|Parotoid gland secretions of toad species are a vast reservoir of bioactive molecules with a wide range of biological properties.
METHODS AND RESULTS:
Herein, for the first time, it is described the isolation by preparative reversed-phase HPLC and the structure elucidation by NMR spectroscopy and/or mass spectrometry of nine major bufadienolides from parotoid gland secretions of the Cuban endemic toad Peltophryne fustiger: ψ-Bufarenogin, gamabufotalin, Bufarenogin, arenobufagin, 3-(N-suberoylargininyl) marinobufagin, bufotalinin, telocinobufagin, marinobufagin and bufalin. In addition, the secretion was analyzed by UPLC-MS/MS which also allowed the identification of azelayl arginine. The effect of arenobufagin, bufalin and ψ-Bufarenogin on Na(+)/K(+)-ATPase activity in a human kidney preparation was evaluated. These bufadienolides fully inhibited the Na(+)/K(+)-ATPase in a concentration-dependent manner, although arenobufagin (IC50 = 28.3 nM) and bufalin (IC50 = 28.7 nM) were 100 times more potent than ψ-Bufarenogin (IC50 = 3020 nM).
These results provided evidence about the importance of the hydroxylation at position C-14 in the bufadienolide skeleton for the inhibitory activity on the Na(+)/K(+)-ATPase.
|Biocatalysis, 2011, 29(2-3):96-101. |
|Biotransformation of arenobufagin and cinobufotalin by Alternaria alternata.[Reference: WebLink]|
|The biotransformation of arenobufagin (1) and cinobufotalin (2), isolated from the natural medicine Chan Su, by Alternaria alternata AS 3.4578 was carried out.
METHODS AND RESULTS:
Incubation of 1 and 2 afforded six metabolites: 3-oxo-arenobufagin (1a), ψ-Bufarenogin (1b), 3-oxo-ψ-Bufarenogin (1c), 3-oxo-Δ4-derivative of cinobufotalin (2a), 3-oxo-cinobufotalin (2b) and 12β-hydroxycinobufotalin (2c). Among them, metabolites 1a, 1c and 2c are new compounds and their structures were characterized on the basis of their spectroscopic data (NMR, MS and IR).
Compounds 1, 2, 1b, 2a and 2b were evaluated for their cytotoxicity against HepG2 and MCF-7 human cancer cells, and all of them showed significant inhibitory activities.