Effects of Digitoxigenin, Digoxigenin, and Various Cardiac Glycosides on Cardenolide Accumulation in Shoot Cultures ofDigitalis lanata

Abstract

Various cardenolide genins and cardenolide glycosides were administered to light-grown and dark-grown Digitalis lanata shoot cultures to investigate conversion reactions related to the formation and rearrangement of the sugar side chain of Digitalis glycosides. Digitoxigenin was converted to digitoxigen-3-one, 3-epidigitoxigenin, and digoxigenin. In addition, various cardiac glycosides were formed, including mono-glycosides with glucose, glucomethylose, fucose, and digitalose, as well as the corresponding diglycosides, all containing a terminal glucose. Digitoxosylated cardenolides were not formed, although the light-grown shoot cultures were capable of producing these compounds. Exogenous cardenolide fucosides were not converted into cardenolide digitoxosides. Administration of evatromonoside (digitoxigenin monodigitoxoside) did not force the formation of cardenolide di- or tridigitoxosides. Our results support the hypothesis that cardenolide fucosides and digitoxosides are formed via different biosynthetic routes and that cardenolide genins can be fucosylated but not digitoxosylated, indicating that digitoxosylation may only occur at an earlier stage in the cardenolide pathway.

Production of the Cytotoxic Cardenolide Glucoevatromonoside by Semisynthesis and Biotransformation of Evatromonoside by a Digitalis lanata Cell Culture

“…This was also reported for digitoxin glycosylation using the same cell culture [25]. GEV concentration decreased after 7 days, probably as a result of degradation [27,30]. A series of attempts were carried out to increase the biotransformation efficacy.…”

“…Depending on their chemical structure, exogenous cardenolides may undergo glycosylation/deglycosylation and acetylation/deacetylation reactions in the side chain, along with hydroxylation of the steroid scaffold [27][28][29]. Although several glycosylation reactions such as glucosylation, fucosylation and digitalosylation were reported to take place in D. lanata tissue cultures [30], digitoxosylation of digitoxigenin has not yet been reported to occur in vivo in plant tissue cultures. Therefore, we did not aim at the production of evatromonoside using a biotransformation process.…”

The Foxgloves (Digitalis) Revisited

“…Digitalis roots cultivated in vitro are not capable of producing cardenolides, although they do contain these compounds in planta, indicating that the root is a sink organ for cardenolides [6,45]. Suspension-cultured Digitalis cells, e.g., [6,44,46], as well as roots or shoots cultivated in vitro, e.g., [6,47], are able to take up exogenous cardenolides and modify them. Biotransformation of appropriate precursors can also yield cardenolides that are not available commercially (see Munkert et al [48], in this issue).…”

Cardenolides from Saussurea stella with Cytotoxicity toward Cancer Cells

“…With the exception of compound 3 , which has a two-sugar chain including a terminal glucopyranosyl moiety, compounds 1 – 10 are linked to a single 6-deoxyhexose moiety. While the aglycons of these cardenolides isolated from S. stella are common, the common 6-deoxyhexoses including quinovose, , fucose, – and xylose ,– are not frequently encountered among cardenolides. Moreover, the cardenolides reported herein have been isolated from a plant in the Asteraceae family for the first time.…”