3-Epidigitoxigenin

Effects of digitoxigenin, digoxigenin, and various cardiac glycosides on cardenolide accumulation in shoot cultures of Digitalis lanata.[Pubmed:17253315]

Planta Med. 1998 Dec;64(8):705-10.

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.

Synthesis and biological evaluation of 2-hydroxy derivatives of digitoxigenin and 3-epidigitoxigenin.[Pubmed:9839018]

Bioorg Med Chem. 1998 Oct;6(10):1889-94.

The four stereoisomers of the 2-hydroxy derivatives of digitoxigenin and 3-Epidigitoxigenin have been synthesized, their structures established by NMR, and their binding affinity for the digitalis receptor on Na+, K(+)-ATPase evaluated. These derivatives showed lower affinities than the parent compounds. The hydrophilic hydroxy groups in the alpha position are more detrimental to the affinity than hydroxy groups in the beta position.

Hydroxysteroid sulfotransferase and a specific UDP-glucuronosyltransferase are involved in the metabolism of digitoxin in man.[Pubmed:1448185]

Naunyn Schmiedebergs Arch Pharmacol. 1992 Aug;346(2):226-33.

In vitro experiments were performed with cytosolic and microsomal fractions of human liver specimens in order to investigate which enzyme forms of sulfotransferase (ST) and UDP-glucurosyltransferase (GT) are involved in the metabolism of digitoxin (dt-3) and/or its cleavage products. It was found that the cytosolic STs preferentially react with digitoxigenin (dt-0) whereas microsomal GTs conjugate digitoxigenin-monodigitoxoside (dt-1) and in traces the bisdigitoxoside (dt-2). Dt-3 and dt-0 cannot be glucuronidated. By separation of different sulfotransferases it was found that the hydroxysteroid-ST is responsible for dt-0 and 3-Epidigitoxigenin (epi-dt-0) sulfation. The hydroxysteroid-ST could be purified and characterized (apparent Km and Vmax for dt-0 sulfation: approx. 17 mumol/l and 2.7 nmol/min mg protein, respectively). Of various model substrates and endogenous compounds (steroids, bilirubin) none caused a competitive inhibition of the microsomal dt-1 glucuronidation except dt-2 and dt-3. Therefore it can be supposed that a new GT form catalyses this reaction. It is characterized by an extraordinarily high affinity towards dt-1 with Km values ranging between 0.7 and 27 mumol/l.

Biotransformation of digitoxigenin by ginseng hairy root cultures.[Pubmed:1366480]

Phytochemistry. 1990;29(3):837-43.

Five new compounds (three esters and two glycosides) and seven previously reported compounds were isolated as biotransformation products of digitoxigenin by ginseng hairy root cultures. The new esters and glycosides were elucidated as digitoxigenin stearate, digitoxigenin palmitate, digitoxigenin myristate, 3-Epidigitoxigenin beta-D-gentiobioside and digitoxigenin beta-D-sophoroside using 1H and 13CNMR and FAB mass spectral data. Biotransformations involving esterification (of stearic acid, palmitic acid, myristic acid and lauric acid) and glycosylation (of gentiobiose and sophorose) of digitoxigenin have been demonstrated for the first time in the plant cell and tissue cultures. The hairy roots showed high glycosylation ability to the digitoxigenin molecule.

Stability of mixed function oxidases in frozen rabbit liver.[Pubmed:1153887]

Res Commun Chem Pathol Pharmacol. 1975 Jul;11(3):467-74.

Little information is available on the effect of storage on hepatic mixed function oxidases. Livers from male New Zealand White rabbits were excised, frozen and maintained at -74 degrees C. Assays were conducted immediately on samples of unfrozen liver (day 0) and on thawed samples of the frozen liver at days 49, 92, 142, 181, and 221. Influence of storage on microsomal protein content, aniline hydroxylase activity, cytochrome P-450, and metabolism of digitoxigenin were determined at each time point. After day 92, homogenates gradually began losing the ability to metabolize digitoxigenin to 6beta-hydroxy-3-Epidigitoxigenin, with 50% of the original activity at day 221. The amount of 3-Epidigitoxigenin increased after day 92 in an amount equal to the loss of formation of 6beta-hydroxy-3-Epidigitoxigenin. Microsomal protein content, aniline hydroxylase activity, and cytochrome P-450 content did not significantly change over the course of 221 days.