Abstract
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 IC50 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 CC50 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 CC50 encouraging further studies of this compound as a trichomonacidal agent.
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Data availability
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
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Funding
This study was partially financed by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brazil (CAPES)—Finance Code 001—Ph.D. Scholarship (MSDA, grant number 88882.346971/2019–01).
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Conceptualization: Mirna Samara Dié Alves, Ângela Sena-Lopes, Sibele Borsuk; Methodology: Mirna Samara Dié Alves, Ângela Sena-Lopes, Angela Maria Casaril; Investigation: Mirna Samara Dié Alves, Raquel Nascimento das Neves, Emerson Teixeira da Silva, Angela Maria Casaril, Micaela Domingues, Paloma Taborda Birmann; Formal analysis: Mirna Samara Dié Alves; Writing – original draft: Mirna Samara Dié Alves; Writing – review & editing: All authors; Project administration: Mirna Samara Dié Alves, Ângela Sena-Lopes, Sibele Borsuk; Supervision: Ângela Sena-Lopes, Sibele Borsuk; and Resources: Emerson Teixeira da Silva, Marcus Vinicius Nora de Souza, Lucielli Savegnago, Sibele Borsuk.
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Alves, M.S.D., Sena-Lopes, Â., das Neves, R.N. et al. In vitro and in silico trichomonacidal activity of 2,8-bis(trifluoromethyl) quinoline analogs against Trichomonas vaginalis. Parasitol Res 121, 2697–2711 (2022). https://doi.org/10.1007/s00436-022-07598-1
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DOI: https://doi.org/10.1007/s00436-022-07598-1