Acetylene Acetogenin from Porcelia macrocarpa Exhibits Superior Efficacy against Schistosoma mansoni In Vivo.

Schistosomiasis affects nearly 250 million people, primarily in low-income regions. Aligned with the Sustainable Development Goals, the WHO roadmap highlights the urgent need for new therapeutic alternatives to praziquantel, the only available drug for schistosomiasis treatment. Natural products, including γ-lactones from Annonaceae species, have shown promising anthelmintic activity. The present work aimed to investigate the anthelmintic potential of the natural acetogenin 3-hydroxy-4-methylene-2-(n-eicos-11'-yn-19'-enyl)-but-2-enolide (HMB) isolated from Porcelia macrocarpa seeds, against Schistosoma mansoni . HMB was characterized by NMR and ESI-HRMS analysis, and its toxicity was assessed using mammalian cell lines and Caenorhabditis elegans. HMB exhibited schistosomicidal activity in vitro (EC5 0 = 19.3-24.6 μg/mL) with no detectable toxicity. in vivo, a single oral dose of 400 mg/kg resulted in a 92.9% reduction in worm burden, which exceeded the 88.2% reduction achieved with praziquantel. Additionally, a 94-100% reduction in egg burden was achieved. Remarkably, the efficacy of HMB was maintained at lower doses. For example, a 65% reduction in worm burden was achieved at 100 mg/kg, whereas praziquantel achieved only 15% at the same dose. Therefore, HMB from P. macrocarpa exhibits potent antischistosomal efficacy in vivo, supporting their further development as promising candidates for schistosomiasis therapy.