Therapeutic prospects of Annona crassiflora based on in vitro and in silico approaches

Abstract

The Annona genus , known for its edible fruits and medicinal properties, includes a unique species, Annona crassiflora . Native to the Brazilian cerrado, this species is traditionally used in folk medicine and has been reported to exhibit antioxidant, laxative, and cytogenotoxic activities. This study investigated the phytochemical profile of the hydroalcoholic fraction of A. crassiflora leaves and evaluated its in vitro antioxidant, acetylcholinesterase (AChE), and tyrosinase inhibitory activities, as well as its in silico potential targets for its flavonoids. The phytochemical profile was analyzed by HPLC-ESI(+)-QTOF-MS/MS, and in silico predictions were performed using the in-house Active-IT system, in which approximately 4,000 high-quality predictive models based on Support Vector Machine (SVM) and Naïve Bayes algorithms. Fifteen compounds, including flavonoid glycosides and flavan-3-ols, were tentatively identified. The fraction exhibited significant antioxidant activity comparable to that of gallic acid and potent AChE inhibitory activity, whereas tyrosinase inhibition was moderate. Active-IT predictions indicated potential biological activities and molecular targets associated with several pharmacological areas, including antimalarial, antitumor, antiviral, and neurodegenerative disease-related activities. Overall, the findings highlight the chemical diversity and biological potential of the hydroalcoholic fraction of A. crassiflora leaves and identify predicted activities and molecular targets that warrant further experimental investigation. Further in vitro and in vivo studies are recommended to validate these findings and explore the new therapeutic targets.