THE CHEMOTHERAPY OF RODENT MALARIA .43. FENOZAN B07 (FENOZAN-50F), A DIFLUORINATED 3,3'-SPIROCYCLOPENTANE 1,2,4-TRIOXANE - COMPARISON WITH SOME COMPOUNDS OF THE ARTEMISININ SERIES

Fenozan B07, a difluorinated 3,3'-spirocyclopentane 1,2,4-trioxane, is a novel, second-generation antimalarial endoperoxide which is a poten t blood schizontocide against strains of rodent malaria that are highl y resistant to a wide spectrum of classical antimalarials. Like compou nds of the artemisinin series, its action is limited to the intra-eryt hrocytic stages, both asexual and sexual, and it is devoid of causal p rophylactic activity. Both Fenozan B07 and the artemisinins are potent gametocytocides. In contrast to arteether, in a model using synchrono us infection with Plasmodium vinckei petteri, Fenozan B07 inhibits the development of all asexual stages except preschizonts, as well as gam etocytes. The activity of the artemisinin series in rodent-malaria mod els is limited to the rings and young trophozoites. The combined effec t of Fenozan B07 with artesunate against P. v. petteri was only additi ve. A slight degree of potentiation was found in mice infected with as ynchronous, drug-sensitive P. berghei but the combination was only add itive against CQ-resistant P. yoelii sap. NS. On the other hand, a sig nificant degree of synergism was observed when mice infected with the artemisinin-resistant ART line of P. yoelii ssp. NS received combinati ons of Fenozan B07 with artemisinin. The conclusion is drawn from thes e and other data that there are significant differences between the bl ood schizontocidal actions of Fenozan B07 and the artemisinins. The ba sis of these differences remains to be determined.