New Orally Active Artemisinin Dimer Antimalarials

摘要

Objective: To synthesize orally bioavailable artemisinin dimers and the evaluation of their in vivo antimalarial activity. Methods: Artemsisin dimers were synthesized and their antimalarial activity was determined in in vitro and in vivo studies (administered orally and IP). Results: Dimers 5 and 6 provided 100% suppression of parastemia throughout the oral administration study, with all animals surviving up to day 28 (the last day of the study). Conclusion: Dimers 4?7 displayed markedly improved in vitro activity against P. falciparum, while the in vivo activity against P. berghei was highly encouraging, with 5 and 6 completely clearing parasitemia from the start of the drug treatment until the end of the study (day 28).