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

  • ACS Omega. 2025 Jul 11;10(28):31161-31169. doi: 10.1021/acsomega.5c05451.
Thainá R Teixeira  1 ,  Bernd Schmidt  2 ,  Eric Sperlich  2 ,  Bruna L Lemes  1 ,  Monique C Amaro  1 ,  Rebeca Pérez  3 ,  Camilo Céspedes-Méndez  3 ,  Cecilia Villegas  4 ,  Viviana Burgos  5 ,  Josué de Moraes  1  6 ,  Cristian Paz  7
Affiliations
  • 1. Research Center on Neglected Diseases, Guarulhos University, Guarulhos, SP 07023-070, Brazil.
  • 2. Institut für Chemie, Universität Potsdam, Karl-Liebknecht-Str. 24-25, Potsdam D-14476, Germany.
  • 3. Carrera de Química y Farmacia, Facultad de Ciencias de la Salud, Universidad Autónoma de Chile, Avenida Alemania 01090, Temuco 4780000, Chile.
  • 4. Departamento de Ciencias Biológicas y Químicas, Facultad de Recursos Naturales, Universidad Católica de Temuco, Rudecindo Ortega, Temuco 4780000, Chile.
  • 5. Escuela de Tecnología Médica, Facultad de Salud, Universidad Santo Tomás, Temuco 4780000, Chile.
  • 6. Research Center on Neglected Diseases, Scientific and Technological Institute, Brazil University, São Paulo, SP 08230-030, Brazil.
  • 7. Laboratory of Natural Products & Drug Discovery, Center CEBIM, Department of Basic Sciences, Faculty of Medicine, Universidad de La Frontera, Temuco 4780000, Chile.
PMID: 40727742 DOI: 10.1021/acsomega.5c05451
Abstract

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.

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