N-Cinnamoylation of Antimalarial Classics: Effects of Using Acyl Groups Other than Cinnamoyl toward Dual-Stage Antimalarials

• Autor(a) principal: Ana Gomes
• Data de Publicação: 2015
• Outros Autores: Marta Machado, Lis Lobo, Fatima Nogueira, Miguel Prudencio, Catia Teixeira, Paula Gomes
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: https://hdl.handle.net/10216/82125
• topic: Medicina básica; Basic medicine

In a follow-up study to our reports of N-cinnamoylated chloroquine and quinacrine analogues as promising dual-stage antimalarial leads with high in vitro potency against both blood-stage Plasmodium falciparum and liver-stage Plasmodium berghei, we decided to investigate the effect of replacing the cinnamoyl moiety with other acyl groups. Thus, a series of N-acylated analogues were synthesized, and their activities against blood- and liver-stage Plasmodiumspp. were assessed along with their in vitro cytotoxicities. Although the new N-acylated analogues were found to be somewhat less active and more cytotoxic than their N-cinnamoylated counterparts, they equally displayed nanomolar activities in vitro against blood-stage drug-sensitive and drug-resistant P.falciparum, and significant in vitro liver-stage activity against P.berghei. Therefore, it is demonstrated that simple N-acylated surrogates of classical antimalarial drugs are promising dual-stage antimalarial leads.