Carbohydrate Component to Physiological Activity

New glycosides are not standardized directly in terms of therapeutic effectiveness in man, but are assayed for toxicity to animals. Because the cat heart behaves toward the drugs in much the same manner as does the human heart, the cat assay has for some time been accepted as the standard. A particularly reliable assay has been developed by K. K. Chen, formerly of the Lilly Research Laboratories, and currently of the Indiana University Medical School. 

Practically all of the known cardenolides have been assayed by Chen and his coworkers the data were obtained in one laboratory under conditions as nearly identical as possible. It is for this reason that meaningful results can best be obtained from this method, particularly for comparison studies in terms of structure-activity relationships. Also, it is important to note that the potency figures for cats are applicable to man, when the drugs are administered intravenously. The data cited in Table I are all Chen assay values those obtained prior to 1961 may be found in an excellent compilation by Hoch.1 Cardenolides, for which assay figures have since been given by Chen, will be referenced accordingly. 

Of the sixteen isomeric aldohexoses, only D-glucose has been found as a carbohydrate component of cardenolides. It generally occurs in combination with other sugars, and rarely are cardenolides found in which a d-glucose residue is joined directly to the aglycon moiety.6 Prior to the work 

Perhaps the strongest support for the argument, that enhancement of cardiotonic activity by the carbohydrate component is a function of hydroxylation, may be gained by inspection of the potencies of the completely deoxygenated 3-tetrahydropyranyl derivatives of digitoxigenin (1) and of strophanthidin (2) (see Table I). In each case, the value ob- 

Pyranosyl moiety Formula of cardenolide LD/Vmole References 

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