Estrutura molecular e atividade biológica de metabólitos secundários de espécies de Vismia Vand (Hypericaceae)

Abstract

Vismia species are producers of anthraquinones, xanthones, terpenoids, lignins and flavonoids and have activities such as: antioxidant, antibacterial, cytotoxic, leishmanicide, antimalarial, among others. Thus, this study aimed to conduct the chemical and biological study of three species of the genus Vismia (V. japurensis, V. cauliflora and V. sandwithii). Three collections of V. japurensis, one from V. sandwithii and one from V. cauliflora were performed. The materials were dried, ground and extracted with hexane, methanol and water. The hexane extracts of the three species were subjected to a comparison of the chemical profile by comparative thin layer chromatography (CCDC) and hydrogen nuclear magnetic resonance (1H NMR). The hexane extracts of the species V. japurensis and V. sandwithii were submitted to several chromatographic fractionations. Structural determination of the isolated substances was performed using spectroscopic methods (1H and 13C NMR, including two-dimensional techniques: HSQC, HMBC, COSY and NOESY) and mass spectrometry, as well as comparison with literature data. Extracts and substances isolated from the species V. japurensis were evaluated for their potential toxicity against Artemia salina, antioxidant, antimalarial, antibacterial and antioangiogenic. By analyzing the chemical profile of the three species of Vismia it was possible to verify the presence of anthraquinones, triterpenes and flavonoids, both by CCDC and NMR analyzes. From the phytochemical study of hexane extracts of V. japurensis leaves, were isolated, two triterpenes (friedelina and friedelan-3--ol) and three anthraquinones (madagascin, fisciona and vismiaquinone A). From the hexane extract of the species V. sandwithii, were isolated, a triterpene (friedelin), an anthraquinone (fiscione) and a steroid (-sitosterol). Regarding the activities performed with the leaves extracts of Vismia japurensis were observed: antioxidant activity of MEOH extracts, with an equivalence of 1.620, considered active for the extract of the first collection and with an equivalence of 3.133, considered average activity for the extract of the second. when compared to the ascorbic acid standard. Regarding antimalarial activity, the hexane extract from the second collection was considered active at a concentration of 5 g/mL with 97.19% inhibition of parasitemia in relation to drug free control. Regarding the toxicity activity against Artemia salina, the hexane extracts of the two collections presented a toxicity in the concentration of 1000 g/mL, with 100% mortality of the larvae. For the antiangiogenic activity, the hexane extract from the second collection showed an activity at a concentration of 500 g/mL, and the isolated substances showed a good antiangiogenic activity, with inhibition above 60% at a concentration of 50 g/mL. For antibacterial activity extracts from the first and second collection were considered active with MIC of 500 g/mL against bacteria Staphylococcus aureus, Klebsiella pneumoniae, Citrobacter freundii, Acinetobacter baumanni, Staphylococcus epidermidis. The isolated substances were evaluated and the triterpene friedelin presented activity against the bacterium Citrobacter freundii at a concentration of 125 g/mL, inhibiting more than 50% of the bacterial growth in relation to the control. These are the first reports of biological activities for the species V. japurensis, and the first report of the isolation of anthraquinones madagascina and supervises in this species. This is also the first chemical study conducted with V. sandwithii.