The present study describes the use of the traditional species Copaifera for treating wounds, such as ulcers scarring and antileishmanial wounds. It also relates phytochemical studies, evaluation of the leishmanicidal activity, and toxicity. The species of Copaifera with a higher incidence in the Amazon region are Copaifera officinalis, Copaifera reticulata, Copaifera multijuga Hayne. The copaiba oil is used in the Amazon's traditional medicine, especially as anti-inflammatory ingredient, in ulcers healing, and in scarring and for leishmaniasis. Chemical studies have shown that these oils contain diterpenes and sesquiterpenes. The copaiba oil and terpenes isolated have antiparasitic activity, more promising in the amastigote form of L. amazonensis. This activity is probably related to changes in the cell membrane and mitochondria. The oil showed low cytotoxicity and genotoxicity. Furthermore, it may interfere with immune response to infection and also has a healing effect. In summary, the copaiba oil is promising as leishmanicidal agent.

Chemotherapy is limited in the treatment of leishmaniasis due to the toxic effects of drugs, low efficacy of alternative treatments, and resistance of the parasite. This work assesses the in vitro activity of flavopereirine on promastigote cultures of Leishmania amazonensis. In addition, an in silico evaluation of the physicochemical characteristics of this alkaloid is performed. The extract and fractions were characterized by thin-layer chromatography and HPLC-DAD, yielding an alkaloid identified by NMR. The antileishmanial activity and cytotoxicity were assayed by cell viability test (MTT). The theoretical molecular properties were calculated on the Molinspiration website. The fractionation made it possible to isolate a beta-carboline alkaloid (flavopereirine) in the alkaloid fraction. Moreover, it led to obtaining a fraction with greater antileishmanial activity, since flavopereirine is very active. Regarding the exposure time, a greater inhibitory effect of flavopereirine was observed at 24 h and 72 h (IC50 of 0.23 and 0.15 μg/mL, respectively). The extract, fractions, and flavopereirine presented low toxicity, with high selectivity for the alkaloid. Furthermore, flavopereirine showed no violation of Lipinski’s rule of five, showing even better results than the known inhibitor of oligopeptidase B, antipain, with three violations. Flavopereirine also interacted with residue Tyr-499 of oligopeptidase B during the molecular dynamics simulations, giving a few insights of a possible favorable mechanism of interaction and a possible inhibitory pathway. Flavopereirine proved to be a promising molecule for its antileishmanial activity.

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Senna reticulata (Willd.) H. S. Irwin & Barneby é uma planta da família Leguminosae nativa da Amazônia, conhecida como “matapasto” ou “folha de pajé”, é utilizada como alimento, medicinamento e outros usos pelas populações da região. Mas para ela faltam informações sobre seus constituintes, assim como sobre várias outras espécies de plantas amazônicas ainda pouco estudadas. Assim, esta pesquisa teve como objetivo revelar a composição química do aroma das flores e folhas de S. reticulata na Amazônia Oriental. Porque tais informações ainda não haviam sido apresentadas para a espécie, e podem ser úteis para sua melhor compreensão. O aroma das flores houve predominância de Geraniol (30,28%), Citronelol (27,87%) e Salicilato de Metila (12,91%). Já o aroma das folhas foi caracterizado por uma mistura de 2E-Hexenal (5,0%) + Hex-(3Z)-enol (67,82%), e por Salicilato de Metila (9,81%) e para-vinilGuaiacol (6,14%). As informações aqui apresentadas poderão contribuir para o desenvolvimento de produtos, com base na composição química do aroma em flores e folhas de S. reticulata, bem como para futuras pesquisas.

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The alkaloids isolated from Zanthoxylum rhoifolium have demonstrated great pharmacological potential; however, the toxic profiles of these extracts and fractions are still not well elucidated. This study evaluated the toxicity of the ethanol extract (EEZR) and neutral (FNZR) and alkaloid (FAZR) fractions. Chemical characterization was performed by chromatographic methods: thin-layer chromatography (TLC) and high-performance liquid chromatography coupled with diode array detection (HPLC–DAD). The cytotoxicity of the samples was evaluated in human hepatocellular carcinoma (HepG2) cells using the cell viability method (MTT) and mutagenicity by the Allium cepa assay (ACA). Alkaloids isolated from the species were selected for toxicity prediction using preADMET and PROTOX. The molecular docking of the topoisomerase II protein (TOPOII) was used to investigate the mechanism of cell damage. In the EEZR, FNZR, and FAZR, the presence of alkaloids was detected in TCL and HPLC–DAD analyses. These samples showed a 50% inhibitory concentration (IC50) greater than 400 μg/mL in HepG2 cells. In ACA, time- and concentration-dependent changes were observed, with a significant reduction in the mitotic index and an increase in chromosomal aberrations for all samples. Nuclear sprouts and a micronucleus of the positive control (PC) were observed at 10 µg/mL and in the FAZR at 30 µg/mL; a chromosomal bridge in FNZR was observed at 105 µg/mL, CP at a concentration of 40 µg/mL, and nuclear bud and mitotic abnormalities in the EEZR were observed at 170 µg/mL. The alkaloids with a benzophenanthridine were selected for the in silico study, as structural alterations demonstrated certain toxic effects. Molecular docking with topo II demonstrated that all alkaloids bind to the protein. In summary, the fractionation of Z. rhoifolium did not interfere with toxicity; it seems that alkaloids with a benzophenanthridine nucleus may be involved in this toxicity.

This study evaluated the genotoxicity of Ethanol Extract (EEEp), Dichloromethane Fraction (FDCMEp) and isoeleutherin isolated from Eleutherine plicata, using the micronucleus test and the impact of structural alterations on toxicity and molecular docking (topoisomerase II and DNA complex). The extract was obtained by maceration and fractionation in a chromatography column. The genotoxicity was evaluated by the micronucleus test in human hepatoma cells (HepG2). Isoeleutherin was the starting molecule in the search for analogues by structural similarity, using the ZINC and e-Molecules databases. Isoeleutherin and analogues were subjected to in silico toxicity prediction, and compounds free of toxicological risks (CP13, CP14, CP17 and isoeleutherin) were selected for molecular docking in Topoisomerase II (PDB: 1ZXM). In the micronucleus test, isoeleutherin was less genotoxic. Among the 22 isoeleutherin analogues there were variations in the toxicity profile. Molecular docking studies showed that the compounds have good complementarity in the active site with important hydrogens bonds. Therefore, the structural changes of isoeleutherin led to the obtaining of a molecule with a lower mutagenic potential, and the CP13 can be considered a prototype compound for the development of new molecules with pharmacological potential.

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