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Toxocara canis: anthelmintic activity of quinone derivatives in murine toxocarosis
T Mata-Santos1, H A Mata-Santos2, P F Carneiro3
1Universidade Federal do Rio Grande - Faculdade de Medicina - Área Interdisciplinar em Ciências Biomédicas - Laboratório de Parasitologia,Rio Grande,Brazil.
Abstract:
Human toxocarosis is a chronic tissue parasitosis most often caused by Toxocara canis. The seroprevalence can reach up to 50%, especially among children and adolescents. The anthelmintics used in the treatment have moderate efficacy. The aim of this study was to evaluate the in vitro and in vivo anthelmintic activity of quinones and their derivatives against T. canis larvae and the cytotoxicity of the larvicidal compounds. The compounds were evaluated at 1 mg mL(-1) concentration in microculture plates containing third stage larvae in an Roswell Park Memorial Institute (RPMI) 1640 environment, incubated at 37 °C in 5% CO2 tension for 48 h. Five naphthoxiranes were selected for the cytotoxicity analysis. The cell viability evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and lactate dehydrogenase assays using murine peritoneal macrophages isolated from C57BL/6 mice revealed that the naphthoxiranes (1 and 3) were less cytotoxic at a concentration of 0.05 mg mL(-1). The efficacy of naphthoxiranes (1 and 3) was examined in murine toxocarosis also. The anthelmintic activity was examined by evaluating the number of larvae in the brain, carcass, liver, lungs, heart, kidneys and eyes. Compound (3) demonstrated anthelmintic activity similar to that of albendazole by decreasing the number of larvae in the organs of mice and thus could form the basis of the development of a new anthelmintic drug.
Insights
New quinone derivatives show promise as effective treatments for human toxocarosis, a parasitic infection affecting many children. Compound (3) demonstrated significant anthelmintic activity in mice, comparable to existing drugs, suggesting potential for new drug development.
Area of Science:
- Parasitology
- Medicinal Chemistry
- Drug Discovery
Background:
- Human toxocarosis, caused by *Toxocara canis*, is a widespread parasitic infection with limited treatment options.
- Current anthelmintics exhibit moderate efficacy, necessitating the search for novel therapeutic agents.
Purpose of the Study:
- To investigate the in vitro and in vivo anthelmintic activity of quinones and their derivatives against *Toxocara canis* larvae.
- To assess the cytotoxicity of potential larvicidal compounds.
Main Methods:
- Compounds were tested in vitro against *T. canis* larvae using Roswell Park Memorial Institute (RPMI) 1640 medium.
- Cytotoxicity was evaluated using MTT and lactate dehydrogenase assays on murine peritoneal macrophages.
- In vivo efficacy was assessed in a murine toxocarosis model by quantifying larvae in various organs.
Main Results:
- Five naphthoxiranes were identified as potential larvicidal compounds.
- Naphthoxiranes (1 and 3) exhibited lower cytotoxicity at 0.05 mg mL(-1).
- Compound (3) demonstrated significant reduction in larval burden in mice, comparable to albendazole.
Conclusions:
- Quinone derivatives, particularly naphthoxirane compound (3), show significant anthelmintic potential against *Toxocara canis*.
- These compounds could serve as a basis for developing new, more effective drugs for human toxocarosis.
