Synthesis of novel 1,2,4-trioxanes and antimalarial evaluation against multidrug-resistant Plasmodium yoelii nigeriensis

Malaria epidemics represent one of the life-threatening diseases to low-income lying countries which subsequently affect the economic and social condition of mankind. In continuation in the development of a novel series of 1,2,4-trioxanes 13a1-c1, 13a2-c2, and 13a3-c3 have been prepared and further converted into their hemisuccinate derivatives 14a1-c1, 14a2-c2, and 14a3-c3 respectively. All these new compounds were evaluated for their antimalarial activity against multidrug-resistant Plasmodium yoelii nigeriensis in mice by both oral and intramuscular (im) routes. Hydroxy-functionalized trioxane 13a1 showed 80% protection and its hemisuccinate derivative 14a1 showed 100% protection at a dose of 48 mg/kg x 4 days by both routes, which is twice active than artemisinin by oral route.

Automated summary

Malaria epidemics pose a threat to low-income countries, and novel 1,2,4-trioxanes have shown promising anti-malarial activity in mice, with some compounds demonstrating twice the efficacy of artemisinin.