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Synthetic camphor derivative (E)-2-((1,7,7-trimethylbicyclo[2.2.1]heptan-2-ylidene)amino)phenol: A novel anthelmintic drug candidate for visceral toxocariasis

Published online by Cambridge University Press:  10 February 2025

D.C. Rodrigues Open the ORCID record for D.C. Rodrigues [Opens in a new window] ,
C.N. de Oliveira da Cunha ,
A.M. Faria ,
V.P. Panassolo ,
L.H.R. Martins ,
M.V.N. de Souza ,
M.C.F.D. de Souza ,
L.S. Munhoz ,
L.F. da Costa de Avila  and
D.F. Ramos
...Show all authors
D.C. Rodrigues*
Affiliation:
Parasitology Laboratory, Faculty of Medicine, Federal University of Rio Grande, Rio Grande, Brazil
C.N. de Oliveira da Cunha
Affiliation:
Parasitology Laboratory, Faculty of Medicine, Federal University of Rio Grande, Rio Grande, Brazil
A.M. Faria
Affiliation:
Parasitology Laboratory, Faculty of Medicine, Federal University of Rio Grande, Rio Grande, Brazil
V.P. Panassolo
Affiliation:
Parasitology Laboratory, Faculty of Medicine, Federal University of Rio Grande, Rio Grande, Brazil
L.H.R. Martins
Affiliation:
Parasitology Laboratory, Faculty of Medicine, Federal University of Rio Grande, Rio Grande, Brazil
M.V.N. de Souza
Affiliation:
Synthesis Department, Institute of Drug Technology, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
M.C.F.D. de Souza
Affiliation:
Sectoral Vivarium, Faculty of Medicine, Federal University of Rio Grande, Rio Grande, Brazil
L.S. Munhoz
Affiliation:
Sectoral Vivarium, Faculty of Medicine, Federal University of Rio Grande, Rio Grande, Brazil
L.F. da Costa de Avila
Affiliation:
Parasitology Laboratory, Faculty of Medicine, Federal University of Rio Grande, Rio Grande, Brazil
D.F. Ramos
Affiliation:
New Drug Development Laboratory, Faculty of Medicine, Federal University of Rio Grande, Rio Grande, Brazil
C.J. Scaini
Affiliation:
Parasitology Laboratory, Faculty of Medicine, Federal University of Rio Grande, Rio Grande, Brazil
*
Corresponding author: D.C. Rodrigues; Email: deboracrvet@gmail.com
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Abstract

Human toxocariasis is a neglected parasitic disease with a global distribution, treated with current anthelmintics that have low to moderate efficacy, and requires the discovery of novel drugs. Camphor derivatives have antimicrobial properties against various pathogens such as fungi and bacteria. This study aimed to identify a camphor derivative with activity against Toxocara canis larvae and evaluate its cytotoxicity, in silico bioavailability, and in vivo activity in Swiss mice infected with this parasite. Three compounds were tested in vitro in duplicate at a concentration of 1.0 to 0.05 mg/mL in a microplate containing 100 T. canis larvae in RPMI-1640 medium incubated for 48 h at 37°C and 5% CO2. The compound (E)-2-((1,7,7-trimethylbicyclo [2.2.1] heptan-2-ylidene)amino)phenol (C2) presented a minimum larvicidal concentration (MLC) of 0.25 mg/mL and was selected for the subsequent steps. This compound showed 100% cell viability in MLC and adequate bioavailability in computational models. Two subsequent in vivo tests were performed on Swiss mice inoculated with 500 T. canis infective eggs through intragastric (IG) intubation, one at 10 days post-inoculation (n=5) and the other at 30 days post-inoculation (n=10). The selected compound (10 mg/kg, via IG) and two controls (albendazole, 40 mg/kg, IG and phosphate buffered saline 0,15M, pH 7,2, via IG) were used for this evaluation. The compound reduced the intensity of infection by 75.7% and 54.8% at 10 and 30 days post inoculation, respectively (p<0.05). The results of this study demonstrate that this compound has potential as an anthelmintic candidate for visceral toxocariasis treatment.

Keywords

Toxocaraparasiticsynthetic compoundcamphorpreclinical trial
Type
Research Paper
Information
Journal of Helminthology , Volume 99 , 2025 , e19
Copyright
© The Author(s), 2025. Published by Cambridge University Press

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