RESUMO
A series of novel 8-aminoquinolines (8-AQs) with an aminoxyalkyl side chain were synthesized and evaluated for in vitro antiplasmodial properties against asexual blood stages, liver stages, and sexual stages of Plasmodium falciparum. 8-AQs bearing 2-alkoxy and 5-phenoxy substituents on the quinoline ring system were found to be the most promising compounds under study, exhibiting potent blood schizontocidal and moderate tissue schizontocidal in vitro activity.
Assuntos
Aminoquinolinas/química , Antimaláricos/química , Plasmodium falciparum/crescimento & desenvolvimento , Aminoquinolinas/síntese química , Aminoquinolinas/farmacologia , Antimaláricos/síntese química , Antimaláricos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Células Hep G2 , Humanos , Estágios do Ciclo de Vida/efeitos dos fármacos , Plasmodium falciparum/efeitos dos fármacos , Relação Estrutura-AtividadeRESUMO
Structural optimization of 3-hydroxy-N'-arylidenepropanehydrazonamides provided new analogs with nanomolar to subnanomolar antiplasmodial activity against asexual blood stages of Plasmodium falciparum, excellent parasite selectivity, and nanomolar activity against the earliest forms of gametocyte development. Particularly, derivatives with a 1,3-dihalo-6-trifluoromethylphenanthrene moiety showed outstanding in vivo properties and demonstrated in part curative activity in the Plasmodium berghei mouse model when administered perorally.