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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., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Trichomoniasis is a great public health burden worldwide and the increase in treatment failures has led to a need for finding alternative molecules to treat this disease. In this study, we present in vitro and in silico analyses of two 2,8-bis(trifluoromethyl) quinolines (QDA-1 and QDA-2) against Trichomonas vaginalis. For in vitro trichomonacidal activity, up to seven different concentrations of these drugs were tested. Molecular docking, biochemical, and cytotoxicity analyses were performed to evaluate the selectivity profile. QDA-1 displayed a significant effect, completely reducing trophozoites viability at 160 µM, with an IC 50 of 113.8 µM, while QDA-2 at the highest concentration reduced viability by 76.9%. QDA-1 completely inhibited T. vaginalis growth and increased reactive oxygen species production and lipid peroxidation after 24 h of treatment, but nitric oxide accumulation was not observed. In addition, molecular docking studies showed that QDA-1 has a favorable binding mode in the active site of the T. vaginalis enzymes purine nucleoside phosphorylase, lactate dehydrogenase, triosephosphate isomerase, and thioredoxin reductase. Moreover, QDA-1 presented a level of cytotoxicity by reducing 36.7% of Vero cells' viability at 200 µM with a CC 50 of 247.4 µM and a modest selectivity index. In summary, the results revealed that QDA-1 had a significant anti-T. vaginalis activity. Although QDA-1 had detectable cytotoxicity, the concentration needed to eliminate T. vaginalis trophozoites is lower than the CC 50 encouraging further studies of this compound as a trichomonacidal agent., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Antimalarial interventions mostly rely upon drugs, as chloroquine. However, plasmodial strains resistant to many drugs are constantly reported, leading to an expansion of malaria cases. Novel approaches are required to circumvent the drug resistance issue. Here, we describe the antimalarial potential of the chloroquine analogue 2-[[2-[(7-chloro-4-quinolinyl)amino]ethyl]amino] ethanol (PQUI08001/06). We observed that PQUI08001/06 treatment reduces parasitemia of both chloroquine-resistant and -sensitive strains of Plasmodium falciparum in vitro and P. berghei in vivo. Our data suggests that PQUI08001/06 is a potential antimalarial therapeutic alternative approach that could also target chloroquine-resistant plasmodial strains.