Estudo fitoquímico e avaliação da atividade biológica in silico e in vitro de Bredemeyera brevifolia

Abstract

This work reports the phytochemical study of the hydromethanolic extract of Bredemeyera brevifolia and the bioactive potential of the extracts. For this, three different approaches were carried out, which are configured in the chapters of this thesis: 1) an integrative review on genus; 2) the phytochemical study and antifungal potential in silico and in vitro; and 3) a study of the application of the response surface methodology in the fractionation of the hexane fraction by CC and HPLC-DAD, in addition to the evaluation of the genotoxic potential of the hydromethanolic extract and hexane fraction by the Allium cepa protocol. The integrative review revealed that the species B. brevifolia, B. floribunda and B. laurifolia were studied from an ethnobotanical point of view, only the extracts and substances of B. floribunda were submitted to some biological assay, while phytochemical studies were carried out with B. brevifolia (where xanthones and fatty acids were identified), and B. floribunda (where xanthones, saponins and a flavonoid were identified). In the phytochemical study of the organic fractions of the leaf extract, from the hexane fraction of B. brevifolia, the methyl esters of the fatty acids were identified: palmitic, margaric, linolelaidic, oleic, stearic, dihomo-g-linolenic and arachidic acid. From the chloroform fraction, the xanthone identified as 1-hydroxy-3,7-dimethoxyxanthone, hitherto unpublished in the genus, was isolated. The hydromethanolic extract was tested for its in vitro antifungal potential against fungal strains from clinical samples resistant to azoles, and it was shown to be active against yeast, filamentous and dermatophyte fungi. In the in silico study, xanthone and fatty acids demonstrated pharmacokinetic potential for the development of phytopharmaceuticals and semi-synthetic analogues with antifungal action. In the study on the application of the response surface methodology, as a chemometric tool, an optimized mobile phase was obtained for the fractionation of the hexane fraction, allowing its semi-purification and subsequent separation of substances by semi-preparative HPLC-DAD. This strategy allowed the isolation of terpenes identified for the first time in the genus: oleanolic acid and ursolic acid, in addition to an unprecedented one, 3β,26,27-trihydroxyolean-12-en-23,28-dioic acid. In the evaluation of the genotoxicity, no abnormalities were observed, indicating that, according to the protocol used, the hydromethanolic extract and the hexane fraction do not present genotoxicity against the A. cepa species.