- Authors: Albuquerque IS, Amewu R, Capela R, Gut J, Lopes F, Marti F, Meireles P, Miranda D, Moreira R, Mota MM, Nogueira F, O'Neill PM, Oliveira R, Paiva I, Prudencio M, Rosenthal PJ
- Publication Year: 2013
- Journal: ACS Medicinal Chemistry Letters
- Link: http://www.ncbi.nlm.nih.gov/pubmed/24900781
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.