Schistosomiasis, a
parasitic disease affecting nearly 250 million individuals globally, poses a significant health challenge. With
praziquantel being the sole available treatment and its limited efficacy in early stage
infections, the identification of novel bioactive compounds becomes imperative. This study examines the potential of
dehydrodieugenol B (1) and its methyl
ether (2), derived from the leaves of the Brazilian Nectandra leucantha plant (Lauraceae), in combatting
Schistosoma mansoni infections through a preclinical approach. Initially, compound 1 displayed noteworthy in vitro
antiparasitic activity with an EC50 of 31.9 μM, showcasing low toxicity in mammalian cells and an in vivo animal model (Caenorhabditis elegans). Conversely, compound 2 exhibited no activity. In silico predictions pointed to favorable oral bioavailability and the absence of PAINS similarities. Subsequently, a single oral dose of 400 mg/kg of compound 1 or
praziquantel was administered to mice infected with adult (patent
infection) or immature parasites (prepatent
infection). Remarkably, in prepatent
infections, 1 resulted in a significant reduction (approximately 50%) in both worm and egg burden, while
praziquantel reduced worm and egg numbers by 30%. The superior efficacy of
dehydrodieugenol B (1) compared to
praziquantel in premature
infections holds the potential to advance the development of new molecular prototypes for
schistosomiasis treatment.