Hybrid products in which the dihydroartemisinin
scaffold is combined with NO-donor furoxan and
NONOate moieties have been synthesized and studied as
potential tools for the treatment of cerebral malaria (CM).
The designed products were able to dilate rat aorta strips
precontracted with phenylephrine with a NO-dependent
mechanism. All hybrid compounds showed preserved
antiplasmodial activity in vitro and in vivo against Plasmodium
berghei ANKA, comparable to artesunate and artemether.
Hybrid 10, selected for additional studies, was capable of increasing survival of mice with late-stage CM from 27.5% to 51.6%
compared with artemether. Artemisinin-NO-donor hybrid compounds show promise as potential new drugs for treating cerebral
malaria.