The resistance of Annona muricata roots to the nematode Meloidogyne javanica was investigated by nuclear magnetic resonance (NMR)-based metabolomics in combination with principal component analysis (PCA). Metabolic changes in roots exposed and not exposed to the nematode were evaluated and compared. In addition, the presence of nematicidal compounds in the root extracts was investigated through in vitro assay against Meloidogyne javanica second-stage juveniles. Plants exposed to nematodes showed significant changes in their metabolism after 24 h. Several resistance-related metabolites, including dopamine, xanthine and aromatic compounds, could be identified in the roots with the joint analysis of 1D/2D NMR and the loadings of PC3 (17.8%). A.muricata root chloroform extract, containing mainly acetogenins, has shown nematostatic activity against M. javanica, suggesting that a pre-formed defense mechanism can support the reported resistance. For the first time, metabolomic studies allowed to identify induced and pre-formed defense mechanisms and their related metabolites in Annona muricata.

The new triterpene friedelan-1,3,21-trione, the known compounds friedelan-3-one, 3β-friedelinol, 3,4-seco-friedelan-3-oic acid, 28-hydroxyfriedelan-3-one, friedelan-3-oxo-28-al, friedelan-3,21-dione, 30-hydroxyfriedelan-3-one, a mixture of 30-hydroxyfriedelan-3-one/21α-hydroxyfriedelan-3-one, 21β-hydroxyfriedelan-3-one, gutta-percha, squalene, and a mixture of palmitic/stearic/oleic acids were isolated from the hexane extracts of leaves and branches of T. micrantha. Their chemical structures were established by Fourier transform infrared spectroscopy (FTIR), gas chromatography (GC), 1D/2D nuclear magnetic resonance (NMR) and comparison with the literature data. All compounds were described for T. micrantha and the genus Tontelea for the first time. The branch and leaf extracts displayed anti-Zika virus activity at the lowest tested concentration of 15.6 µg mL-1, mainly virucidal effect, and presented no cytotoxicity to Vero cells. Furthermore, the ethyl acetate and methanolic leaf extracts demonstrated the best activities at the concentration of 31.2 and 15.6 µg mL-1 at the viral adsorption and penetration stages, respectively. These results showed that these extracts may be promising candidates for the Zika virus treatment.

Annona cornifolia A. St. -Hil. é uma pequena árvore anual perene encontrada no cerrado brasileiro; seu fruto verde é usado popularmente no tratamento de úlceras. As acetogeninas isoladas a partir das sementes de Annona cornifolia anteriormente apresentaram atividade antioxidante. Continuando as nossas investigações sobre as atividades biológicas das acetogeninas, quatro misturas binárias e dez acetogeninas bis-tetra-hidrofurânicas adjacentes puras foram avaliadas quanto às atividades: citotóxica (sobre três linhagens de células tumorais humanas), antifúngica (sobre Paracoccidioides brasiliensis), tripanocida (sobre Trypanosoma cruzi) e leishmanicida (sobre Leishmania amazonensis). As acetogeninas apresentaram atividade citotóxica, confirmando seu uso potencial na terapia anticâncer. Quanto às atividades leishmanicida e tripanocida, foi observada uma inibição de 87% das formas amastigotas de L. amazonensis e 100% de formas amastigotas e tripomastigotas de T. cruzi, quando testadas a uma concentração de 20 µg mL–1. Além disso, seis acetogeninas mostraram maior atividade sobre todas as três cepas testadas de P. brasiliensis que o trimetoprim-sulfametoxazol, um medicamento usado no tratamento da paracoccidioidomicose. Assim, as acetogeninas podem ser uma alternativa no tratamento de uma série de doenças que têm um enorme impacto em milhões de pessoas no mundo. Este trabalho relata pela primeira as atividades antifúngica, leishmanicida e tripanocida para estas acetogeninas.

Annona cornifolia A. St. -Hil. is a small annual perennial tree found in the Brazilian savannah; their green fruit is popularly used in the treatment of ulcers. The acetogenins isolated from the seeds of Annona cornifolia previously showed to possess antioxidant activity. In continuation of our investigations on the biological activities of acetogenins, four binary mixtures and ten pure adjacent bis-tetrahydrofuran annonaceous acetogenins were evaluated: the cytotoxic (against three human tumor cell lines), antifungal (against Paracoccidioides brasiliensis), trypanocidal (against Trypanosoma cruzi) and leishmanicidal (against Leishmania amazonensis) activities. Acetogenins presented cytotoxic activity confirming their potential use in anti-cancer therapy. Regarding leishmanicidal and trypanocidal activities, an inhibition of 87% of L. amazonensis amastigotes and 100% of T. cruzi amastigotes and trypomastigotes was observed, when tested at the concentration of 20 µg mL–1. Moreover, six acetogenins showed more activity against all the three tested isolates of P. brasiliensis than trimethoprim-sulfamethoxazole, a drug used for treating paracoccidioidomycosis. Thus, acetogenins may be an alternative in treating a number of diseases that have a huge impact on millions of people worldwide. This paper reports for the first time the antifungal, leishmanicidal and trypanocidal activities for these acetogenins.

The phytochemical study of hexane/ethyl ether (1:1) extract of the roots of M. imbricata, Celastraceae, resulted in the isolation and characterization of six known triterpenes: 11α-hydroxylup-20(29)-en-3-one, previously isolated from this species besides, 3β,11α-di-hydroxylup-20(29)-ene, 3,7-dioxofriedelane, 3-oxo-29-hydroxyfriedelane, tingenone and 6-oxo-tingenol. The chemical structures of these triterpenes were established by spectrometric data (IR, ¹H and 13C NMR) and through comparison with literature data. The hexane/ethyl ether (1:1), ethyl acetate and methanol extracts, and 11α-hydroxylup-20(29)-en-3-one, tingenone and 6-oxo-tingenol, showed antimicrobial properties on in vitro assays. All extracts and triterpenes, except 3β,11α-di-hydroxylup-20(29)-ene, presented toxicity demonstrated by the larvicidal effect test using Artemia salina.