Contribuição ao estudo fitoquímico e biológico de espécies de Brosimum da Região Amazônica

Abstract

Despite the wide variety of medicinal plants existing in the Amazon region, many have not been studied regarding their chemical composition and biological activity, especially those belonging to the genus Brosimum (Moraceae), whose species are widely used by local populations. The present work investigated the chemical content of the species B. acutifolium and B. parinarioides present in the Amazon region, as well as evaluated their antioxidant (in vitro) and antitumor (in silico) potential. To achieve this objective, different extracts were prepared based on the design of mixtures with three different organic solvents (DCM, AcOEt, and EtOH), and then submitted for analysis by mass and chemometric spectrometry. Fractions from DCM, AcOEt of B. acutifolium, and AcOEt of B. parinarioides extracts were submitted to modern chromatographic analysis, and the resulting substances were identified by MS, 1D and 2D NMR spectra. The Biological activity of extracts and isolated substances were analyzed by DPPH, FRAP, ABTS, and inhibition assays against the FLT3 protein. In addition, the determination of the total phenolic content of the extracts was also measured. The chemical composition study of the extract DCM:AcOEt of B. acutifolium, showed 7,4′-dihydroxy-8-prenylflavan, 4′-hydroxy-7,8-(2′′,2′-dimethylpyran)flavan, isoliquiritigenin, isobavachalcone, kanzonol B, kanzonol C and corylifol B, with kanzonol B-C reported for the first time in the species and corylifol B in the Moraceae family. On the other hand, the chemical study of the AcOEt and MeOH extracts of B. parinarioides resulted in the isolation of 4',6-dihydroxy-5-prenyl-flavan, 7,8-dimethoxy-2,2-dimethyl-1-benzopyrone- 6-propanoic acid, licoagrachalcone, isoliquiritigenin, 2,4,4'-trihydroxy-5'-(2”-hydroxy-3”-methyl-butenyl)-chalcone and kanzonol B, being new compounds the 4',6-dihydroxy-5-prenyl-flavan, 2,4,4'-trihydroxy-5'-(2”-hydroxy-3”-methyl-butenyl)-chalcone, 7,8-dimethoxy-2,2-dimethyl-1-benzopyrone-6-propanoic acid, named parinarioidins A-C. The study of the total phenolic content showed a high content for the extracts of both species, and the antioxidant potential of the extracts and isolated substances revealed antioxidant activity by DPPH, ABTS, and FRAP radicals. Finally, to analyze the antitumor potential of the substances, a molecular docking study was carried out with the FLT3 protein, where it was possible to observe potential inhibitors for kanzonol B, kanzonol C, licoagrachalcone A, corylifol B, isobavachalcone, 4'-hydroxy- 7,8- (2”,2”-dimethylpiano)flavan, isoliquiritigenin and brosimin B evidenced by higher binding free energy (-10.3 to -9.8 kcal/mol) when compared to the positive control doxorubicin (-8.1 kcal/mol), which was explained by the establishment of favorable interactions between the new ligand-FLT3 complex.