143-62-4Relevant articles and documents
Potential antitumor activity of digitoxin and user-designed analog administered to human lung cancer cells
Dinu, Cerasela Zoica,Dong, Chenbo,Eldawud, Reem,Gupta, Neha,O'Doherty, George,Rojanasakul, Yon,Stueckle, Todd A.,Wagner, Alixandra
, (2020)
Background: Cardiac glycosides (CGs), such as digitoxin, are traditionally used for treatment of congestive heart failure; recently they also gained attention for their anticancer properties. Previous studies showed that digitoxin and a synthetic L-sugar monosaccharide analog treatment decreases cancer cell proliferation, increases apoptosis, and pro-adhesion abilities; however, no reports are available on their potential to alter lung cancer cell cytoskeleton structure and reduce migratory ability. Herein, we investigated the anticancer effects of digitoxin and its analog, digitoxigenin-α-L-rhamnoside (D6MA), to establish whether cytoskeleton reorganization and reduced motility are drug-induced cellular outcomes. Methods: We treated non-small cell lung carcinoma cells (NSCLCs) with sub-therapeutic, therapeutic, and toxic concentrations of digitoxin and D6MA respectively, followed by both single point and real-time assays to evaluate changes in cellular gene and protein expression, adhesion, elasticity, and migration. Results: Digitoxin and D6MA induced a decrease in matrix metalloproteinases expression via altered focal adhesion signaling and a suppression of the phosphoinositide 3-kinases / protein kinase B pathway which lead to enhanced adhesion, altered elasticity, and reduced motility of NSCLCs. Global gene expression analysis identified dose-dependent changes to nuclear factor kappa-light-chain-enhancer, epithelial tumor, and microtubule dynamics signaling. Conclusions: Our study demonstrates that digitoxin and D6MA can target antitumor signaling pathways to alter NSCLC cytoskeleton and migratory ability to thus potentially reduce their tumorigenicity. Significance: Discovering signaling pathways that control cancer's cell phenotype and how such pathways are affected by CG treatment will potentially allow for active usage of synthetic CG analogs as therapeutic agents in advanced lung conditions.
THERMAL TRANSFORMATION OF CARDIAC GLYCOSIDES II. ACIDLESS HYDROLYSIS OF LABILE GLYCOSIDES IN AQUEOUS ALCOHOLIC SOLUTIONS AND PROSPECTS FOR ITS UTILIZATION
Makarevich, I. F.,Tishchenko, A. A.,Terno, I. S.
, p. 53 - 55 (1991)
The thermal transformations of cardiac glycosides in neutral alcoholic solutions have been investigated.The kinetics of their acidless hydrolysis at 100 and 142 deg C and the activation energy of the process have been studied.The possibility has been shown of the stepwise hydrolysis of natural trisdigitoxosides with the production of difficulty available mono- and bisdigitoxosides.The following were used as the objects of investigation: convallatoxin, glucostrophanthidin, cheirotoxin, desglucocheirotoxin, erycordin, erysimin, erysimoside, digitoxin, and cymarin.
Does the malonyl-coenzyme A:21-hydroxypregnane 21-hydroxy-malonyltransferase catalyze the first step in the formation of the butenolide ring of cardenolides?
Stuhlemmer,Kreis
, p. 2221 - 2224 (1996)
An enzyme catalyzing the transfer of the malonyl moiety from malonyl-coenzyme A 1 to the 21-hydroxy group of 3β, 14β, 21-trihydroxy-5β-pregnane-20-one 2 was isolated from Digitalis lanata leaves and characterized. The role of this particular enzyme in cardenolide biosynthesis is discussed.
GLYCOSYLATED CARDIOTONIC STEROIDS
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Paragraph 0188, (2014/12/12)
Compounds which are glycosylates of an A-ring of a cardiotonic steroid, wherein the steroid is attached to the anomeric position of (a) a monosaccharide comprising a C-4 amino group, or (b) an oligosaccharide are provided.
Assembly of digitoxin by gold(I)-catalyzed glycosidation of glycosyl o-alkynylbenzoates
Ma, Yuyong,Li, Zhongzhen,Shi, Hefang,Zhang, Jian,Yu, Biao
body text, p. 9748 - 9756 (2012/01/04)
Digitoxin, a clinically important cardiac trisaccharide, was assembled efficiently from digitoxigenin and 3,4-di-O-tert-butyldiphenylsilyl-d- digitoxosyl o-cyclopropylethynylbenzoate in 9 steps and 52% overall yield via alternate glycosylation and protecting group manipulation. The present synthesis showcases the advantage of the gold(I)-catalyzed glycosylation protocol in the synthesis of glycoconjugates containing acid-labile 2-deoxysugar linkages.
Digitoxigenin-3-O-β-D-glucopyranoside from the roots of Sapium sebiferum
Bose, Chandana
experimental part, p. 1252 - 1254 (2012/01/13)
The plant Sapium sebiferum is commonly known as Vilayati shisham in Hindi and belongs to natural order Euphorbiaceae. The plant is widely cultivated in India. The ethyl acetate soluble fraction of the concentrated ethyl alcohol soluble part of its roots when subjected to column chromatography yielded a yellow coloured compound, m.f. C29H44O9, m.p. 200-201 °C [α]D -19.3°, M+ = 536, which on various chemical degradations, colour reactions and spectral analysis was identified as digitoxigenin-3-O-β-D-glucopyranoside AC-4.
GLYCOSIDE COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS THEREOF
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Page/Page column 22, (2010/04/03)
The present invention provides glycoside compounds, methods of preparing such compounds, pharmaceutical compositions comprising such compounds, and a method for the treatment of hyperproliferative diseases using the same.
Enantioselective total synthesis of (+)-digitoxigenin
Honma, Masahiro,Nakada, Masahisa
, p. 1541 - 1544 (2008/02/03)
An enantioselective total synthesis of (+)-digitoxigenin is described. This total synthesis is accomplished in a convergent manner using two chiral fragments prepared via the catalytic asymmetric intramolecular cyclopropanation and baker's yeast mediated reduction developed by us, respectively. This convergent synthesis would be useful for preparing some new derivatives of digitoxigenin for SAR studies and could be applied for the total synthesis of other cardenolides left unprepared.
Ketoimines of cardenolides
Makarevich,Gubin,Megges
, p. 52 - 55 (2007/10/03)
3-Keto-derivatives of the cardenolides digitoxigenin and cardiogenin were prepared with subsequent conversion to new ketoimines (1-19, 24-44), the oxime (23), and for the first time to pure cardiogenin (14,16-dianhydrogitoxigenin, 20), its acetate (21), and cardiogenone (22). Their physicochemical properties were described. 2005 Springer Science+Business Media, Inc.
