Antiplasmodial action and chemical constitution Part I. Cinchona alkaloidal derivatives and allied substances

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Abstract
The constitution of the cinchona alkaloids is known with certainty, and some have been synthesized, but little is known as to why they are antiplasmodial in action. The introduction of experimental bird malaria has given a means of following changes in therapeutic activity with changes in chemical structure, and mainly through the work of Giemsa, Weise and Tropp (1926), Goodson, Henry and Macfie (1930), Schönhöfer (1933), Giemsa and Oesterlin (1933) and Buttle, Henry and Trevan (1934), some insight has been gained of the effect of simple changes of structure of the cinchona alkaloids on their antiplasmodial action in bird malaria. The present communication, in extension of the work of these observers, is designed primarily to furnish additional data which might provide a working hypothesis for further experiments. The chief naturally occurring cinchona alkaloids are embraced by the formula (I): where R may be H or OMe, R1 may be .CH:CH2 or .CH2.CH3 and R2 is OH, and so far as the results of their therapeutic examination on bird malaria due to Plasmodium praecox or inconstans have been recorded by previous workers they are all active. We have prepared seven chloroalkaloids (I, R2 = Cl) by the action of phosphorus pentachloride on the hydrochloride of the bases (Comstock and Königs 1884) and, of these chloro-derivatives, hydrocinchonidine chloride has not been previously described. The following table shows that on the doses tried they were all inactive when tested orally on PI. relictum (= Pl. praecox) in canaries, and this result amplifies a similar observation of Giemsa, Weise and Tropp (1926) on chloroquinine.