Biotransformation of Cinobufagin by Cunninghamella elegans

Abstract

Cunninghamella elegans has been employed for the biotransformation of cinobufagin to afford 5 metabolites. The structures of the transformation products have been characterized as 12a -hydroxybufagin, 11a -hydroxybufagin, 12b-hydroxy-desacetylcinobufagin, 3-oxo12a -hydroxybufagin and 12b -hydroxybufagin. Products 12a -hydroxybufagin and 11a -hydroxybufagin are new compounds. In vitro both the biotransformation products and cinobufagin all showed cytotoxic activities against HeLa cells.

Bufadienolides with cytotoxic activity from the skins of Bufo bufo gargarizans

“…4). The small Flack parameter of 0.16 (15) allowed unambiguously determination of the absolute stereochemistry. As a result, the structure of 11 was established as (3α,5β,14β)-3,11,14-trihydroxy-12-oxo-bufa-9(11),20,22-trienolide.…”

“…

Twelve new bufadienolides (1-12), along with fourteen known analogues (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26) were isolated from the skins of Bufo bufo gargarizans CANTOR. Their chemical structures were elucidated on the basis of NMR, HRESIMS and X-ray diffraction analysis.

…”

Microbial biotransformation as a tool for drug development based on natural products from mevalonic acid pathway: A review

“…Resibufogenin was converted to 3-acetyl-resibufogenin and 3-acetyl 15 β -hydroxyl bufotalin, which showed significantly increased cytotoxic activity than the substrate, while cinobufagin and bufalin were converted to 3-acetyl cinobufagin and 3-acetyl bufalin respectively, in which the biotransformation reaction showed great regio-selectivity on bufadienolides. On the other hand, when Cunninghamella elegans was employed for the biotransformation of cinobufagin, 5 metabolites including 12 α -hydroxybufagin, 11 α -hydroxybufagin, 12 β -hydroxydesacetylcinobufagin, 3-oxo-12 α -hydroxybufagin and 12 β -hydroxybufagin were produced [57] .…”

A Microbial Transformation Model for Simulating Mammal Metabolism of Artemisinin

“…In recent years, microbial transformations have become powerful routes for metabolic simulations [21], and have been used to study metabolism of a variety of clinical drugs, such as fenofibrate [22], imipramine [23], monensin A [24], and cinobufagin [25]. Compared with in vivo metabolism studies and microsomal methods, microbial transformation is more convenient and cost-effective, especially with the advantage of scalability in vitro.…”