Novel endoperoxide-based transmission-blocking antimalarials with liver- and blood-schizontocidal activities

Daniela Miranda, Rita Capela, Inês S. Albuquerque, Patrícia Meireles, Isa Paiva, Fátima Nogueira, Richard Amewu, Jiri Gut, Philip J. Rosenthal, Rudi Oliveira, Maria M. Mota, Rui Moreira, Francesc Marti, Miguel Prudêncio, Paul M. O'Neill, Francisca Lopes

Research output: Contribution to journalArticlepeer-review

35 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)108-112
Number of pages5
JournalACS Medicinal Chemistry Letters
Volume5
Issue number2
DOIs
Publication statusPublished - 13 Feb 2014

Keywords

  • Antimalarials
  • endoperoxide
  • P. berghei
  • sporogonic cycle

UN Sustainable Development Goals (SDGs)

  • SDG 3 - Good Health and Well-Being

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