Larvicidal activity of coumarin derivatives on Toxocara canis larvae, cytotoxicity analysis, and in silico bioavailability studies.
Anthelminthic
Coumarin
Parasite
Synthetic compound
Toxocariasis
Journal
Parasitology research
ISSN: 1432-1955
Titre abrégé: Parasitol Res
Pays: Germany
ID NLM: 8703571
Informations de publication
Date de publication:
19 Jun 2024
19 Jun 2024
Historique:
received:
06
04
2024
accepted:
13
06
2024
medline:
19
6
2024
pubmed:
19
6
2024
entrez:
19
6
2024
Statut:
epublish
Résumé
Human toxocariasis is a neglected anthropozoonosis with global distribution. Treatment is based on the administration of anthelmintics; however, their effectiveness at the tissue level is low to moderate, necessitating the discovery of new drug candidates. Several groups of synthetic compounds, including coumarin derivatives, have demonstrated bioactivity against fungi, bacteria, and even parasites, such as Dactylogyrus intermedius, Leishmania major, and Plasmodium falciparum. The aim of this study was to evaluate the effect of ten coumarin-derived compounds against Toxocara canis larvae using in vitro, cytotoxicity, and in silico tests for selecting new drug candidates for preclinical tests aimed at evaluating the treatment of visceral toxocariasis. The compounds were tested in vitro in duplicate at a concentration of 1 mg/mL, and compounds with larvicidal activity were serially diluted to obtain concentrations of 0.5 mg/mL; 0.25 mg/mL; 0.125 mg/mL; and 0.05 mg/mL. The tests were performed in a microculture plate containing 100 T. canis larvae in RPMI-1640 medium. One compound (COU 9) was selected for cytotoxicity analysis using J774.A1 murine macrophages and it was found to be non-cytotoxic at any concentration tested. The in silico analysis was performed using computational models; the compound presented adequate results of oral bioavailability. To confirm the non-viability of the larvae, the contents of the microplate wells of COU 9 were inoculated intraperitoneally (IP) into female Swiss mice at 7-8 weeks of age. This confirmed the larvicidal activity of this compound. These results show that COU 9 exhibited larvicidal activity against T. canis larvae, which, after exposure to the compound, were non-viable, and that COU 9 inhibited infection in a murine model. In addition, COU 9 did not exhibit cytotoxicity and presented adequate bioavailability in silico, similar to albendazole, an anthelmintic, which is the first choice for treatment of human toxocariasis, supporting the potential for future investigations and preclinical tests on COU 9.
Identifiants
pubmed: 38896311
doi: 10.1007/s00436-024-08272-4
pii: 10.1007/s00436-024-08272-4
doi:
Substances chimiques
Coumarins
0
Anthelmintics
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
246Informations de copyright
© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
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