Constituintes Químicos e Investigação do Potencial Citotóxico das cascas e folhas de Guatteria olivacea (Annonaceae)

Abstract

Guatteria olivacea R. E. Fries is an Amazonian species belonging to the Annonaceae family popularly known as “araticum”, “ata” and “envireira”, which occurs in rainforest solid ground with distribution in Brazil, particularly in the states of Amazonas and Pará. According to the literature, there are no records of chemical and pharmacological studies about it. Thus, in this work, the phytochemical study and in vitro cytotoxicity of the crude extracts, fractions and isolated substances of the bark, and of the essential oil of G. olivacea leaves were performed. The study of the bark resulted in the isolation and characterization of ten substances belonging to the class of alkaloids, two obtained in a mixture. For the isolation of the chemical constituents classical chromatographic techniques (CC and CCDP) was performed and for the identification of these constituents spectroscopic (1H and 13C 1D/2D) and spectrometric (MS) techniques was used. The isolated and identified alkaloids belong to the subclasses of aporphines (asimilobine, puterine and discoguattine), oxoaporphines (liriodenine and oxoputerine), phenanthrenes (atherosperminine, argentinine and atherosperminine N-oxide) and tetrahydroprotoberberines (corypalmine and discretine). All identified alkaloids are reported in the genus but unprecedented in the species investigated, with phenanthrene alkaloids being the least occurring. Among all bark extracts (hexane and methanolic) and fractions submitted to the in vitro cytotoxic activity assay, the alkaloid fraction from the methanolic extract showed the highest activity against the evaluated tumor cell lines, with IC50 values of 20.16 μg. mL-1 for MCF-7 and 18.25 μg.mL-1 for HepG2. Among the isolated alkaloids that were evaluated, atherosperminine presented the best results against MCF-7, HCT116, HepG2 and HL-60 cell lines with IC50 values of 41.10, 33.07, 42.10 and 33.79 μmol.L-1, respectively. The essential oil extracted from the leaves was analyzed by GC-DIC and GC-MS and presented as major constituents sesquiterpenes germacrene D (17.65%), β-atlantol (13.21%), caryophyllene oxide (12.03%), spatulenol (11.26%) and (E)-caryophyllene (7.26%). Cytotoxic evaluation of this oil showed promising activity against MCF-7, HCT116, HepG2, and HL-60 tumor cell lines with IC50 values of 27.22, 25.74, 34.95 and 16.11 μg.mL-1, respectively. The obtained results corroborate the chemical and cytotoxic potential of the Brazilian Annonaceae species, in particular of the species occurring in the Amazonas, and justify the continuity of their study in future projects in search of substances with cytotoxic properties.