Stage-Dependent Anthelmintic Activity of Licarin A Against the Neurotropic Nematode Angiostrongylus cantonensis

Angiostrongylus cantonensis is the leading cause of eosinophilic meningitis worldwide, but therapeutic options remain limited. This study investigated the anthelmintic activity and preliminary selectivity of licarin A, a neolignan isolated from Nectandra oppositifolia. The compound was evaluated in vitro against first-stage (L1) larvae, infective third-stage (L3) larvae, and adult worms, using albendazole as the reference drug. Cytotoxicity was assessed in mammalian kidney epithelial, keratinocyte, and neuronal cell models, while whole-organism toxicity was examined in Caenorhabditis elegans. Physicochemical, pharmacokinetic, drug-likeness, and toxicological properties were also predicted computationally. Licarin A was active against L1 and L3 larvae, with EC50 values of 16.8 and 36.4 µM, respectively. Its activity was comparable to albendazole against L1 but lower against L3, and no relevant effect was observed against adult worms (EC50 > 100 µM). No detectable cytotoxicity or lethality was observed in the mammalian cell lines or C. elegans at concentrations up to 500 µM. Computational analyses indicated favorable drug-likeness, high gastrointestinal absorption, blood–brain barrier permeation, lack of recognition as a P-glycoprotein substrate, and generally low predicted toxicity. These findings identify licarin A as a selective, stage-dependent anthelmintic hit and provide a foundation for optimization of its scaffold against parasitic nematodes.