Novel Endoperoxide-Based Transmission-Blocking Antimalarials with Liver- and Blood-Schizontocidal Activities

作者：Miranda Daniela; Capela Rita; Albuquerque Ines S; Meireles Patricia; Paiva Isa; Nogueira Fatima; Amewu Richard; Gut Jiri; Rosenthal Philip J; Oliveira Rudi; Mota Maria M; Moreira Rui; Marti Francesc; Prudencio Miguel; O'Neill Paul M; Lopes Francisca^*

来源：ACS Medicinal Chemistry Letters, 2014, 5(2): 108-112.

DOI：10.1021/ml4002985

• Antimalarials
• endoperoxide
• sporogonic cycle
• P. berghei

In a search for effective compounds against both the blood- and liver-stages of infection by malaria parasites with the ability to block the transmission of the disease to mosquito vectors, a series of hybrid compounds combining either a 1,2,4-trioxane or 1,2,4,5-tetraoxane and 8-aminoquinoline moieties were synthesized and screened for their antimalarial activity. These hybrid compounds showed high potency against both exoerythrocytic and erythrocytic forms of malaria parasites, comparable to representative trioxane-based counterparts. Furthermore, they efficiently blocked the development of the sporogonic cycle in the mosquito vector. The tetraoxane-based hybrid 5, containing an amide linker between the two moieties, effectively cleared a patent blood-stage P. berghei infection in mice after i.p. administration. Overall, these results indicate that peroxide-8-aminoquinoline hybrids are excellent starting points to develop an agent that conveys all the desired antimalarial multistage activities in a single chemical entity and, as such, with the potential to be used in malaria elimination campaigns.

• 出版日期2014-2
• 单位河北医科大学