Spathulenol, a Sesquiterpene from Guarea macrophylla, Displays Potent and Selective Anthelmintic Activity against Angiostrongylus cantonensis.

Helminth infections remain among the most prevalent neglected tropical diseases worldwide, with angiostrongyliasis representing an emerging zoonotic condition associated with eosinophilic meningitis. In this study, spathulenol, a sesquiterpene isolated from Guarea macrophylla (Meliaceae), was evaluated for its anthelmintic potential using first-stage larvae (L1) of Angiostrongylus cantonensis as a phenotypic screening model. Spathulenol exhibited pronounced in vitro activity against L1 larvae, with an EC50 value in the low micromolar range (7.6 μM), outperforming the reference drug albendazole (15.1 μM) and showing slightly higher potency than pyrantel pamoate (10.4 μM) under identical experimental conditions. Phenotypic, morphological, and morphometric analyses further revealed compound-specific effects on parasite larvae, supporting biological differentiation from reference anthelmintics. This activity was accompanied by a favorable selectivity profile, as no cytotoxic effects were observed in human and animal cell lines at concentrations well above those required for antiparasitic activity (CC50 >200 μM). Moreover, spathulenol did not induce lethality in the free-living nematode Caenorhabditis elegans at concentrations up to 1000 μM. Taken together, these findings identify spathulenol as a selective hit compound emerging from phenotypic screening, representing a promising scaffold for early-stage anthelmintic drug discovery.