Bertholletia excelsa Bonpl. (Lecythidaceae) is a South American tree worldwide known for providing the Brazil nuts. In the Amazon Region, B. excelsa is found in monocultures, integrating agroforestries and providing raw materials for food and timber industries. Through the application of an integrative analysis based on high-performance liquid chromatography coupled with diode array detector and tandem mass spectrometry (HPLC-DAD-MS/MS) and nuclear magnetic resonance (NMR) techniques, the present study showed that B. excelsa bark biomass residues contain large quantities of ellagic acid (EA) and its derivatives. Qualitatively, five compounds were characterized for the first time in this species. Quantitations were carried out to determine the total amount of these compounds in outer and inner bark tissues. A total of 4.96 and 44.09 g of EA derivatives per kg of dry residues was determined for the outer and inner barks, respectively. Among the EA derivatives, eschweilenol C, ellagic acid and valoneic acid dilactone were the main compounds. These results pointed B. excelsa barks as a valuable biomass residue with potential to be source of health-promoting compounds. Therefore, a potential raw material as source of valuable bioactive phenolic compounds is described herein.

In the present study, in vitro techniques were used to investigate a range of biological activities of known natural quassinoids isobrucein B (1) and neosergeolide (2), known semi-synthetic derivative 1,12-diacetylisobrucein B (3), and a new semi-synthetic derivative, 12-acetylneosergeolide (4). These compounds were evaluated for general toxicity toward the brine shrimp species Artemia franciscana, cytotoxicity toward human tumour cells, larvicidal activity toward the dengue fever mosquito vector Aedes aegypti, haemolytic activity in mouse erythrocytes and antimalarial activity against the human malaria parasite Plasmodium falciparum. Compounds 1 and 2 exhibited the greatest cytotoxicity against all the tumor cells tested (IC50 = 5-27 µg/L) and against multidrug-resistant P. falciparum K1 strain (IC50 = 1.0-4.0 g/L) and 3 was only cytotoxic toward the leukaemia HL-60 strain (IC50 = 11.8 µg/L). Quassinoids 1 and 2 (LC50 = 3.2-4.4 mg/L) displayed greater lethality than derivative 4 (LC50 = 75.0 mg/L) toward A. aegypti larvae, while derivative 3 was inactive. These results suggest a novel application for these natural quassinoids as larvicides. The toxicity toward A. franciscana could be correlated with the activity in several biological models, a finding that is in agreement with the literature. Importantly, none of the studied compounds exhibited in vitro haemolytic activity, suggesting specificity of the observed cytotoxic effects. This study reveals the biological potential of quassinoids 1 and 2 and to a lesser extent their semi-synthetic derivatives for their in vitro antimalarial and cytotoxic activities.

Infusões dos caules de Picrolemma sprucei (pseudônimo: P. pseudocoffea) são principalmente utilizadas como antimaláricos em toda região amazônica. Desta espécie foram isolados os quassinoides isobruceína B e neosergeolida, os quais apresentam atividade antimalárica e citotóxica. Neste estudo, apresentamos o desenvolvimento de uma metodologia analítica por LC-(+)-ESI-MS/MS visando a determinação dos principais quassinoides desta espécie. O método desenvolvido foi empregado para análise de uma formulação artesanal (infusão de 1 g de matéria seca - caules pulverizados de P. sprucei em 1 L de água fervente). Padrões previamente isolados de isobruceína B e neosergeolida foram utilizados para a determinação da linearidade na faixa de calibração entre 0,25 to 5 µg mL-1 e 0,5 a 10 µg mL-1, respectivamente. Como padrão interno foi utilizada a substância fluoroglucinol na concentração de 4,0 µg mL-1. Ambos os compostos apresentaram boa linearidade, precisão e exatidão e as concentrações de isobruceína B e neosergeolida obtidas nas infusões foram de 60,1 e 774 µg L-1, respectivamente.

Infusions of the stems of Picrolemma sprucei (pseudonym: P. pseudocoffea) are used in the Amazon regions of Peru, Brazil and French Guiana as antimalarials among other uses. They contain the bitter quassinoids isobrucein B (1) and neosergeolide (2) that have important antimalarial and toxic properties among others. In this study, an LC-(+)-ESI-MS/MS method was developed and applied to the determination of 1 and 2 in a common remedy prepared by infusing 1 g of dry, powdered stems of P. sprucei in 1 L of boiling water. Isolated 1 and 2 were used in calibration ranges of 0.25 to 5 µg mL-1 and 0.5 to 10 µg mL-1, respectively, with the internal standard phloroglucinol at 4.0 µg mL-1. Good linearity, precision and accuracy were observed for both compounds. The concentrations of 1 and 2 in the stem infusions were found to be 60.1 and 774 µg L-1, respectively.

In the present study, a quassinoid, neosergeolide, isolated from the roots and stems of Picrolemma sprucei (Simaroubaceae), the indole alkaloids ellipticine and aspidocarpine, isolated from the bark of Aspidosperma vargasii and A. desmanthum (Apocynaceae), respectively, and 4-nerolidylcatechol, isolated from the roots of Pothomorphe peltata (Piperaceae), all presented significant in vitro inhibition (more active than quinine and chloroquine) of the multi-drug resistant K1 strain of Plasmodium falciparum. Neosergeolide presented activity in the nanomolar range. This is the first report on the antimalarial activity of these known, natural compounds. This is also the first report on the isolation of aspidocarpine from A. desmanthum. These compounds are good candidates for pre-clinical tests as novel lead structures with the aim of finding new antimalarial prototypes and lend support to the traditional use of the plants from which these compounds are derived.