Estudo químico e avaliação da atividade anticolinesterásica dos alcaloides isolados da casca do fruto de Annona crassiflora

Abstract

Annona crassiflora, popularly known as marolo or araticum, is a native Cerrado tree commonly used in cookery and traditional medicine for the treatment of scalp infections, diarrhea and combating lice. This species belongs to the Annonaceae family, which is recognized by the presence of flavonoids, acetogenins and alkaloids, mostly of the benzylisoquinolinic type. Annona is one of the most relevant genera of the family, because it presents a great diversity of alkaloids, of recognized pharmacological potential. In this work was made the chemical study of the Annona crassiflora fruit peels. Initially the ethanolic extract was prepared, which was subjected to liquid-liquid extraction with solvents of increasing polarity. The fractions were evaluated by CCD and revealed with iodocloroplatinate, noting that higher concentration of alkaloids in the CH2Cl2 fraction. This fraction was subjected to different chromatographic procedures (CC and CLAE), which resulted in the isolation of the aporphines alkaloids stephalagine (I), liriodenine (II) and atherospermidine (III), that have their structures elucidated by spectrometric (MS) and spectroscopic techniques (NMR). In addition to the isolated compounds, dehydroroemerine (IV), dehydroestephalagine (V) and xylopine (VI) were identified through ESI-MS and MS-IE analyzes. Thus the ethanolic extract, the alkaloid fraction and I were submitted to the in vitro anticholinesterase assay, in which I showed good results with the enzymes AChE (IC50 39.8 ± 6.3 μM) and BChE (IC50 104.2 ± 20, 6 μM) when compared to the positive control galantamine (IC50 5.0 ± 0.3 μM and 162.7 ± 28.8 μM). The isolated compounds were evaluated in the in silico assay (molecular docking), which showed that aporphine alkaloids interact with AChE and BChE in the same region as inhibitors such as huprin W and galantamine. These results reveal the importance of these compounds as models for the development of new drugs for the treatment of diseases related to the central nervous system as Alzheimer’s disease.