Princípios Antimaláricos de Croton cajucara Benth. (Euphorbiaceae)

Abstract

Malaria is one of the most important endemic diseases in tropical regions whose treatment is based on substances discovered from plants traditionally used in folk medicine. Thus, faced with the resistance of the parasite (Plasmodium spp.), The search for new drugs has become fundamental. Among the bioactive substances of plant species, terpenoids have a range of biological activities, among which antimalarial. Therefore, the objective of this research was the isolation of substances with antimalarial potential. The species that are indicated as antimalarial and that was used in the present study is easily found and is also cultivated in the State of Amazonas in EMBRAPA and INPA: 'sacaca' (Croton cajucara Benth). Croton cashews and leaves of Benth (Euphorbiaceae) were submitted for the preparation of bioactive extracts, with relevance in the antimalarial activity. In the in vitro bioassay of the P. falciparum K1 strain, IC50 = 6.4 ± 1.2 μg / mL, followed by the ethanolic extract of the bark, with IC 50 = 17.2 ± 6.6. The extracts were investigated by means of a traditional phytochemical approach, based on the open column chromatographic fractionation, resulting in the isolation of seven substances. Natural substance 1 was acetylated in a reaction of acetic anhydride (Ac 2 O) and pyridine (C 5 H 5 N), resulting in compound 2. These eight compounds were identified primarily by 1 H and 13 C 1 D and 2 D and CL-EMAR NMR analyzes. The results showed that only three compounds had inhibition above 50% (1, 2 and 6), but the compound (1) and (2) 6) showed better activity by inhibiting more than 80% of in vitro growth of P. falciparum strain K1: 70.5-68.0 (1); 63.9-55.6 (2); 57.6-0 (3); 41.8-37.2 (4); 18.6-23.2 (5); 92.7-75.6 (6); 34.9-23.2 (7) and 37.2-11.6 (8). 1 and 6 had their IC50 calculated, where they presented moderate in vitro activity against P. falciparum strain, with IC 50 = 23.7 and 23.0 μg / mL, respectively. Compound 1 was the only one to be tested in vivo, however it did not show activity against P. berghei, orally and subcutaneously during the seven day treatment period.