Cubebin, a Lignan Isolated from Drimys andina, Exhibits Potent and Selective Antiparasitic Activity against...

Angiostrongylus cantonensis is a zoonotic parasitic nematode of growing global health concern, largely due to the limited efficacy of current anthelmintics such as albendazole. In this study, cubebina dibenzylbutyrolactole lignanwas isolated for the first time from Drimys andina (Winteraceae), a Chilean endemic plant, and evaluated for its antiparasitic activity. Chromatographic purification of fresh leaves yielded cubebin as a 3:2 epimeric mixture, with its structure confirmed by 500 MHz NMR and single-crystal X-ray diffraction. In vitro assays demonstrated potent anthelmintic activity against both first-stage (L1) and infective third-stage (L3) larvae of A. cantonensis, with EC₅₀ values of 4.7 and 15.3 μM, respectively, making it approximately three times more potent than albendazole against L1 and comparably effective against L3. Cubebin exhibited no cytotoxicity toward monkey (Vero) or human (HaCaT) cell lines and no toxicity in Caenorhabditis elegans, indicating a favorable safety profile. In silico ADME analysis further revealed favorable pharmacokinetic and drug-likeness properties. These results highlight cubebin as a promising lead compound for the development of novel anthelmintic therapies targeting A. cantonensis and potentially other parasitic nematodes.