The Chemotherapy of Malaria

Abstract

OUININE was discovered by Pelletier and Caventou in 1820 and was promptly manufactured in France and England in quantities sufficient to permit of its use in the treatment of malaria, in place of crude cinchona bark. This was an early and unconscious application of the principle upon which Ehrlich was to found chemotherapy ninety years later. By that time, thanks to the labours of Hesse, Skraup, Koenigs, von Miller and Rohde and Rabe, constitutional formulae had been assigned to quinine and the other cinchona alkaloids, which Rabe and his collaborators confirmed in a series of researches culminating in the complete synthesis of dihydro-quinine and dihydroquinidine in 1931. Partial syntheses had been effected some years earlier and the methods employed had been extended to the preparation of products allied to the cinchona alkaloids in type, but of simpler structure. In 1891 Grimaux and Arnaud prepared from cupreine a series of homologues of quinine, one of which, ethylcupreine, was tried clinically and found to be somewhat more active than quinine, and this first French experiment in the production of ‘modified cinchona alkaloids' led to the preparation of many other substances of this type.