Anotação de alcaloides isoquinolinos de espécies de Annonaceae por espectrometria de massas e redes moleculares

Abstract

The Annonaceae family is widely distributed in Brazil, mainly in the Amazon region, where its species are used in folk medicine to treat different diseases, such as leishmaniasis, malaria and diabetes. In addition, scientifically, many biological properties have already been conferred on the family, such as cytotoxic, antioxidant, anti-inflammatory, antinociceptive and antiparasitic. These properties are mainly attributed to the presence of secondary metabolites, such as isoquinoline alkaloids, widely reported in the genera. Based on this, this work describes a chemical investigation of this class of alkaloids in six species of Annonaceae from the Amazon region, as well as proposes fragmentation patterns to help in the chemical characterization of these metabolites. For this, experiments were carried out via liquid chromatography coupled to high resolution mass spectrometry and the acquired MS/MS spectra were analyzed by molecular network approach. The results revealed molecular families composed of aporphine alkaloids, benzylisoquinolines, tetrahydroprotoberberines and oxoaporphines, and 30 compounds were annotated at level 2. The characterization of the structures was further explained by the manual analysis of the fragmentation spectra, allowing propagation of 30 manual annotations of alkaloids at level 3. Among the known molecules, anonaine, asimilobin and liriodenine were mutually noted in D. calycina, G. olivacea, P. leiophylla and E. amazonicus, reinforcing the chemophenetic relevance of these alkaloids to the Annonaceae family, as well as the close relationship between genera Duguetia and Guatteria. The results obtained corroborate that the six species studied are excellent producers of isoquinoline alkaloids, especially the aporphines, a ubiquitous class in the family. The fragmentation study with the 7,7-dimethylaporphine alkaloids that present unsaturation in the b isoquinoline ring corroborated the studies by Carnevale Neto and his collaborators, revealing the elimination of the methyl radical as the main information. Additionally, fragmentation studies were extended to 7,7- dimethylaporphines that do not show unsaturation in the isoquinoline B ring, as far as we know, reported in this work for the first time.