Ex vivo antimalarial activity and semisynthesis of limonoids isolated from Andiroba (Carapa guianensis).

Plants have been used since antiquity as a therapeutic alternative for the treatment of various diseases. Their therapeutic power comes from the bioactive substances produced as secondary metabolites. From Cinchona officinalis and Artemisia annua were isolated quinine and artemisinin respectively. The isolation of both led to the development of new synthetic and semi synthetic drugs such as chloroquine, artesunate, artemether, and arteether that are used in the malaria treatment nowadays. Among the bioactive substances of plants, limonoids, found in several species of the Meliaceae family, have a rich range of biological activities including antimalarial and insecticide properties. In this work three limonoids were isolated from Carapa guianensis seeds and residual pressed seed material, using solid-liquid extraction, recrystallization techniques, followed by classic column chromatography. The limonoid 7-deacetoxy-7-oxogedunin was isolated from ethyl acetate seed extract. Limonoids 6ɑ-acetoxyepoxyazadiradione and 6ɑ-acetoxygedunin were isolated from the residual pressed seed material acetone extract. Deacetylation and reduction reactions carried out with the isolated limonoids led to four new compounds. Limonoids were characterized by high-resolution mass spectrometry (HRMS) and nuclear magnetic resonance (NMR). The antimalarial activity of 7-deacetoxy-7-oxigedunin and 6α-acetoxyepoxyazadiradione was evaluated using recent isolates of P. vivax collected from patients presenting ++ 2-20 parasites/field (10.001-100.000 p/mm3). To evaluate the antimalarial activity, the maturation of trophozoites into schizonts was observed and followed by counting 200 parasites/field by optic microscopy. Limonoid 7-deacetoxy-7-oxogedunin presented IC50 = 9.44 μg/mL and 6α-acetoxyepoxyazadiradione 2.1 μg/mL. The range of concentrations used to determine the IC50 values were 50 – 0.78 μg/mL. Chloroquine was used as a control drug with IC50 1.7 μg/mL. The antimalarial essay was realized in the Hospital of Tropical Medicine (FMT-HVD) approved by the ethics committee (CAAE 50812815.0.0000.0005). Both limonoids tested shown promising antimalarial activity against P. vivax.