In an attempt to establish whether and to what extent activity as antimalarials and embryotoxicity can be divorced, IC50s for activity in Plasmodium falciparum strains and the NOELs for RBCs were compared. From this comparison, arterolane showed a better safety margin than artemisinin.
Thirty-three N-acyl 1,2,4-dispiro trioxolanes (secondary ozonides) were synthesized. For these ozonides, weak base functional groups were not required for high antimalarial potency against Plasmodium falciparum in vitro, but were necessary for high antimalarial efficacy in Plasmodium berghei-infected mice. A wide range of Log P/DpH 7.4 values were tolerated, although more lipophilic ozonides tended to be less metabolically stable.