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Peer-reviewedCC BYTropical medicine and infectious disease

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

4 affiliations
  1. 1Research Center on Neglected Diseases, Brazil University, Guarulhos 07023-070, SP, Brazil.
  2. 2Interdisciplinary Laboratory of Biosciences, Faculty of Medicine, University of Brasília, Brasília 70910-900, DF, Brazil.
  3. 3Research Center on Neglected Diseases, Scientific and Technological Institute, Brazil University, São Paulo 08230-030, SP, Brazil.
  4. 4Center for Natural and Human Sciences, Federal University of ABC, São Paulo 09210-180, SP, Brazil.

Abstract

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.

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BibTeX
@article{neves2026stagedependent,
  title = {{Stage-Dependent Anthelmintic Activity of Licarin A Against the Neurotropic Nematode Angiostrongylus cantonensis.}},
  author = {Elias L Neves and Lucas Fukui-Silva and Thainá R Teixeira and Davi Luna-Tavares and Felipe S Sales and João Henrique G Lago and Nadjar Nitz and Josué de Moraes},
  journal = {Tropical medicine and infectious disease},
  year = {2026},
  month = sep,
  doi = {10.3390/tropicalmed11100263},
  url = {https://europepmc.org/article/MED/42931447},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Stage-Dependent Anthelmintic Activity of Licarin A Against the Neurotropic Nematode Angiostrongylus cantonensis.
AU  - Elias L Neves
AU  - Lucas Fukui-Silva
AU  - Thainá R Teixeira
AU  - Davi Luna-Tavares
AU  - Felipe S Sales
AU  - João Henrique G Lago
AU  - Nadjar Nitz
AU  - Josué de Moraes
PY  - 2026
DA  - 2026/09/23
JO  - Tropical medicine and infectious disease
DO  - 10.3390/tropicalmed11100263
UR  - https://europepmc.org/article/MED/42931447
AB  - 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.
SN  - 2414-6366
ER  -