Novas abordagens no tratamento da tricomoníase humana e tricomonose animal

Abstract

Trichomonas sp. is a flagellated protozoan that infects humans and birds. Trichomonas vaginalis is the most common non-viral STI (sexually transmitted infection) globally, with women generally exhibiting symptoms more than men, who are often asymptomatic and contribute to the spread of the disease. Trichomonas gallinae infects the upper digestive tract of birds, especially pigeons. Symptoms vary depending on the immunity and virulence of the strain. Nitroimidazoles are used for treatment, but there are cases of reinfection and parasite resistance. Compounds derived from benzofuroxanes (BZX) are widely used in the synthesis of bioactive substances. This study seeks to investigate the antiparasitic efficacy and antioxidant potential of new BZX compounds, as well as their influence on the gene expression of T. vaginalis trophozoites, both in vitro and in silico, aiming at therapeutic alternatives for trichomoniasis. Furthermore, in this study, treatment strategies were explored, through the repurposing of antibiotic drugs from two classes (nitrofurans and fluoroquinolones), in in vitro tests for T. gallinae to evaluate efficacy. To determine the antiparasitic activity in T. vaginalis trophozoites, benzofuroxane compounds called: EH1, EH2, EH3 and H1, EH2, EH3 and EA2). In in silico analysis, the interaction of the compound EH3 with cathepsin-like proteins (TvCPC) and T. vaginalis dehydrogenase (TvLDH) was studied via molecular anchoring.It can be observed that all compounds were effective in vitro with 95% inhibition after 12 hours of experiment and 100% in 24 hours, as well as it was possible to observe interactions of the compound with the proteins lactate dehydrogenase and cathepsin (TvCPC and TvLDH), suggesting that the interaction may be a likely mechanism of action. To better understand this mechanism between BZX compounds and trophozoites, lipid peroxidation analyses, reactive oxygen species assay and .In the analysis of gene expression using important proteins for the survival of T. vaginalis, such as hydrogenase, malic enzyme, pyruvate ferrodoxin-oxide reductase A . It is suggested that the compounds caused damage to the trophozoite membrane, possibly through the production of reactive oxygen species (ROS) and therefore also demonstrated otein modulation, thus suggesting a possible interaction between the compounds and the tested proteins. In tests with T. gallinae, the evaluation of the in vitro antiparasitic activity of the antibiotics Nitrofurantoin (NT), Norfloxacin (NOR) and Ciprofloxacin (CP) were tested against T. gallinae at different concentrations: 5 mg/mL to 0.1 mg/ mL (CP); 10 mg/mL to 0.25mg/mL (NOR) and 5 mg/mL to 0.03 mg/mL (NF). Maximum efficacy was achieved at the highest concentrations within 24 hours, resulting in approximately 100% inhibition of trophozoites. Through the results obtained, it is concluded that the BZX compounds and antibiotics showed promise in in vitro tests for T. vaginalis and T. gallinae, showing promise for the treatment of trichomoniasis and avian trichomoniasis.