Larvicidal activity of coumarin derivatives on Toxocara canis larvae, cytotoxicity analysis, and in silico bioavailability studies

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, incl...

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Published in:Parasitology research (1987) 2024-06, Vol.123 (6), p.246, Article 246
Main Authors: Rodrigues, Débora Carvalho, de Oliveira da Cunha, Carolina Netto, Mattos, Gabriela Torres, Martins, Lourdes Helena Rodrigues, Nogueira, Thais Cristina Mendonça, de Souza, Marcus Vinícius Nora, da Costa de Avila, Luciana Farias, Ramos, Daniela Fernandes, Scaini, Carlos James
Format: Article
Language:English
Subjects:
Albendazole
Animal models
Anthelmintic agents
Bioavailability
Biological activity
Biomedical and Life Sciences
Biomedicine
Coumarin
Cytotoxicity
Drug development
Immunology
Larvae
Larvicides
Macrophages
Mathematical models
Medical Microbiology
Microbiology
Toxocara canis
Toxocariasis
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Summary: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.
ISSN:0932-0113
1432-1955
1432-1955
DOI:10.1007/s00436-024-08272-4