Avaliação da atividade sinérgica in vitro e in vivo de produtos naturais da Amazônia e seus derivados contra Plasmodium Spp

Abstract

Malaria is an infectious and potentially fatal disease that has had a major impact on mankind's historical origins and perpetuates it to the present day. Currently the parasite presents resistance to available drugs, making it urgent to search for and discover new antimalarial molecules. Although it is a major challenge for researchers, the study of medicinal plants is a promising strategy because it provides molecules with pharmacological antimalarial potential, such as 6α-acetoxyglycine (6α-ACG) and diacetylated 4-nerolidylcatechol (4-NCAC2 ), however, first pass metabolism reduces the in vivo antimalarial activity of these drugs. In view of the above, in an attempt to increase the antimalarial activity of the substances, especially in the antimalarial model in vivo, this study aimed to evaluate the synergistic activity in vitro and in vivo of natural products of the Amazonian against Plasmodium spp. For this, the in vitro anti-plasmodial activities, in vitro synergistic and antiplasmodial in vivo were evaluated using 6α-ACG (isolated from Carapa guianensis), its semi-synthetic derivative 6α-hydroxy-deacetylenedunine, the semi-synthetic derivative 4-NCAC2 (isolated Piper peltata) and dilapiol (DIL, isolated from Piper aduncum). The standard strains of P. falciparum K1 were used for the in vitro test, in which the microtest method proposed by Trager & Jensen (1976) was used. The in vitro synergism test culture was preceded by the Trager & Jensen method, however, the proportions of the association of the compounds as well as the classification followed the method described by Odds (2003). In the in vivo tests, strains of P. berghei NK65 were used, using the parasitemia suppression method of Peters (1965). It was possible to observe that DIL does not exert extensive modulatory activity in vitro, but when associated with 6α-ACT or 4-NCAC2 to DIL, the substances have a better IC50. Both the association between 4-NCAC2 and 6α-ACG and 6α-HIDROXI and 6α-ACG were classified as indifferent, that is, they did not present synergistic activity. In this work, as with others, DIL was able to increase inhibition levels of P. berghei parasitemia in association with a limonoid.