Synthesis and In Vivo Antimalarial Evaluation of Novel Hydroxyethylamine Derivatives

Mariana Conceicao de Souza, Triciana Goncalves-Silva, Marcele Moreth, Claudia R.B. Gomes; Carlos Roland Kaiser, Maria das Gracas Muller de Oliveira Henriques, Marcus V.N. de Souza

Abstract

A series of hydroxyethylamines has been synthesized from the reaction of (2S,3S )Boc-phenylalanine epoxide with alkyl amines in good yields and evaluated for their in vivo antimalarial activity in mice. Compound 4g presented better activity then the reference artesunate in percentage of inhibition of parasitemia in treated P. berghei-infected mice and compare to the activity of artesunate in the survival of mice 14 days after infection. In addiction, no hemolytic activity was found, which supports that inhibition of parasitemia is due to antimalarial activity. The compound 4g inhibited the differentiation to schizonts suggesting that parasite metabolism is a possible target of 4g. These results indicate that this class of compound possesses promising perspectives for the development of new antimalarial drugs.

Keywords: Hydroxyethylamine, antimalarial drugs, protease inhibitors, plasmepsin, inhibition, Malaria, diseases, Plasmodium, antimalarials, life cycle