THE CARDIAC ACTION OF THE DERIVATIVES OF STROPHANTHIDIN AND CYMARIN

¹ From the Lilly Research Laboratories, Indianapolis, and the Department of Chemistry, Columbia University, New York City

1. A few derivatives and isomers of strophanthidin and cymarin have been studied in frogs and cats with the aim of determining the relative importance of chemical groupings present in nature.

2. Strophanthidin is about 1/5 as active in frogs and as active in cats as cymarin, showing that splitting of the sugar, cymarose, results in reduction of action.

3. Oxidation of the aldehyde group on C₁₀ of strophanthidin to form strophanthidinic acid is followed by substantial diminution of action—approximately 8 times less active in cats, and 153 times less active in frogs, than strophanthidin.

4. Saturation of the double bond in the side chain is accompanied by practically complete loss of activity as exemplified by dihydrostrophanthidin, dihydrostrophanthidinic acid, and isostrophanthidin. A residual effect may be sometimes demonstrated in sensitive animals, probably due to an intact lactone ring as in the case of dihydrostrophanthidinic acid.

5. The inertness of the sodium salt of saponified isostrophanthidin may be attributed chiefly to the disappearance of the double bond and lactone ring of the side chain.

6. Decrease or loss of action may be also suspected if the OH group on C₁₄ is reacted with another group in the molecule as in the case of pseudostrophanthidin, isostrophanthidin, and the sodium salt of saponified isostrophanthidin.

7. Very marked reduction or often complete loss of activity may occur when stereochemical rearrangement in the steroid ring system has taken place as illustrated by pseudostrophanthidin, allocymarin, allostrophanthidin, and presumably isostrophanthidin. These results indicate clearly that the digitalis-like action of strophanthidin and cymarin depends on not only a side chain with intact, double bond and lactone ring, but also the steroid ring system in favorable spatial isomerism.