Glycosides, cardioactive

Thus, compound SC 4453 (1), a pyridazine analogue of digoxin studied in Belgium, has been shown to have cardioactive properties similar to those of the natural cardiac glycoside [3], 17 -(4-Pyridazinyl)androstane deriva-... 

An important transformation in steroid biochemistry is the conversion of pregnenolone into progesterone. Progesterone is a female sex hormone, a progestogen, but this reaction is also involved in the production of corticosteroids such as hydrocortisone and aldosterone. The reaction also occurs in plants, and features in the formation of cardioactive glycosides, such as digitoxin in foxglove. 

Herbs rich in cardioactive glycosides Alocasia macrorrhiza root tuberf... 

Chemistry of the glycoside linkage. Exceptionally fast and efficient formation of glycosides by remote activation, Carbohydr. Res. 80 07 (1980). (e) K. Wiesner, T. Y. R. Tsai, and H. Jiu, On cardioactive steroids. XVI. Stereoselective P-glycosylation of digitoxose the synthesis of digitoxin, Helv. Chim. Acta 60 300 (1985). (f) R. B. Woodward (and 48 collaborators), Asymmetric total synthesis of erythromycin. 3. Total synthesis of erythromycin, J. Am Chem. Soc. 103 3215 (1981). (g) P. G. M. Wuts and S. S. Bigelow, Total synthesis of oleandrose and the avermecin disaccharide, benzyl ot-L-oleandrosyl-ot-L-4-acetOxyoleandroside, J. Org. Chem. 43 3489 (1983). 

Many other species of Digitalis, e.g. D. dubia, D. ferruginea, D. grandiflora, D. lutea, D. mertonensis, D. nervosa, D. subalpina, and D. thaspi contain cardioactive glycosides in their leaves, and some have been evaluated and cultivated for drug use. 

The dried roots and tops of lily of the valley, Convallaria majalis (Liliaceae/Convallariaceae), contain cardioactive glycosides (0.2-0.3%) and are used in some European countries rather than digitalis. The effects are similar, but the drug is less cumulative. This plant is widely cultivated as an ornamental, particularly for its intensely perfumed small white flowers, and must be considered potentially toxic. The major glycoside (40-50%) is convallatoxin (Figure 5.98), the rhamnoside of strophanthidin. 

Many plants containing cardioactive glycosides are widely grown as ornamentals and must be considered toxic and treated with due care and respect. These include Digitalis species, Convallaria majalis, Helleborus species, and oleander (Nerium oleander, Apocynaceae). 

Other classes of proteins that have been clearly identified as drug receptors include enzymes, which may be inhibited (or, less commonly, activated) by binding a drug (eg, dihydrofolate reductase, the receptor for the antineoplastic drug methotrexate) transport proteins (eg, Na+/K+ ATPase, the membrane receptor for cardioactive digitalis glycosides) and structural pro-teins (eg, tubulin, the receptor for colchicine, an anti-inflammatory agent). 

Biochemical evidence and transfection studies suggest that a and p isoforms can assemble in different combinations and potentially form functional pumps. The sodium pump is specifically inhibited by a series of naturally occurring steroids, such as ouabain (Hansen 1984). Based on their clinical use, these substances are also referred to as cardiac glycosides or cardioactive steroids. Cardiac glycoside sensitivity is conferred by the a subunit of the Na-K-ATPase, and this class of drags is used to treat congestive heart failure (Scheiner-Bobis and Schneider 1997). 

Canadian hemp Apocynum cannabinum Cardioactive glycosides in root and aerial parts Bradycardia, A-V block Less cardiotoxic than foxglove... 

Foxglove Digitalis purpurea Cardioactive glycosides in ripe seeds, leaves, flowers Bradycardia, A-V block, miosis Digitalis ianata is major source of digoxin in the United States. 

Hedge mustard Sisymbrium officinale Cardioactive glycosides in aerial parts Bradycardia, A-V block Avoid confusion with other mustard species... 

Lily of the valley Convallaria majalis Cardioactive glycosides in root, flowers, leaves Bradycardia, A-V block Water from the cut flowers also toxic... 

Monkshood Wallflower Aconitum napellus Cheiranthus cheiri Aconitine in root, leaves, flowers Cardioactive glycosides in ripe seeds and flowers Hypothermia, bradycardia, respiratory arrest Bradycardia, A-V block Fatal adult dose >2 mg topical use also toxic... 

The aldehyde group of cardioactive glycosides and aglycones can also be selectively reduced. Hunger and Reichstein377 carried out such reactions with strophanthidin, convallatoxin, and similar compounds. 

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