In vivo efficacy of uvangoletin from Piper aduncum (Piperaceae) against Schistosoma mansoni and in silico studies targeting SmNTPDases.

Schistosomiasis stands as one of the most significant parasitic diseases on a global scale, with approximately 250 million infections worldwide. It is imperative to address this pressing issue by developing new antischistosomal drugs. Chalcones have emerged as a promising class of natural compounds, demonstrating noteworthy effects observed in vitro experiments with Schistosoma mansoni, and demonstrating the ability to inhibit SmNTPDases and apyrase from potatoes. In this study, we focused on uvangoletin, a naturally occurring dihydrochalcone from Piper aduncum. We isolated uvangoletin from P. aduncum fruits and conducted in vivo experiments to evaluate the efficacy of uvangoletin against adult Schistosoma parasites. Furthermore, we explored the inhibitory effects of uvangoletin on potato apyrase and employed molecular docking analyses to investigate its interactions with apyrase from potato and the two isoforms SmNTPDase 1 and 2 through in silico studies. Uvangoletin (400 mg/kg, p. o.), exhibited significant in vivo antiparasitic effects against adult S. mansoni, leading to a decrease of 53.7% in worm burden and 54.3% in egg production. The treatment also reduced hepatomegaly and splenomegaly. In silico investigations and ADMET studies indicated that uvangoletin possesses favorable drug-like properties and may interact with key residues involved in apyrase and SmNTPDases activities. Furthermore, uvangoletin demonstrated a substantial reduction in potato apyrase activity. These results suggest the potential for exploring other dihydrochalcones as promising candidates for antischistosomal agents.