Article ID Journal Published Year Pages File Type
70029 Journal of Molecular Catalysis B: Enzymatic 2013 6 Pages PDF
Abstract

Cinobufotalin (1), a major bioactive bufadienolide, has the potential anti-cancer activity. In the present paper, a scaled-up biotransformation of 1 by Aspergillus niger AS 3.739 and Alternaria alternate AS 3.4578 was performed for improving its biological activities and water-solubility. Seven metabolites were prepared in the biotransformation process of 1, and their structures were elucidated as 9α-hydroxycinobufotalin (2), 3-oxo-cinobufotalin (3), 5β-hydroxy-3-epi-deacetyl-cinobufagin (4), 5β-hydroxy-deacetylcinobufagin (5), 3-acetoxy-cinobufotalin (6), 5β,15β,16α-trihydroxyl-17βH-bufalin (7) and norbufadienolide A (8), on the basis of extensive spectral data including 2D NMR and MS spectroscopy. Among them, metabolites 2, 7 and 8 are novel, and metabolite 8 possessed a novel chemical skeleton of bufadienolide in nature. The highly stereo- and region-specific dehydrogenation of 1 by A. niger AS 3.739 were observed. While, A. alternate AS 3.4578 could catalyze a novel rearrangement reaction, hydroxylation and acetylation in biotransformation process of 1. In addition, the transformed products (2–8) exhibited the significant antiproliferative activities against human cervical carcinoma (Hela) and human breast cancer (MCF-7) cell lines.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Seven metabolites of cinobufotalin were isolated. ► A. alternate AS 3.4578 could catalyze an unexpected rearrangement of C/D rings. ► HO-9 of 1 by A. niger AS 3.739 was a rare microbial transformation reaction.

Related Topics
Physical Sciences and Engineering Chemical Engineering Catalysis
Authors
, , , , , , , ,