In Vitro and in Silico Trichomonacidal Activity of 2,8-bis(trifluoromethyl) Quinoline Analogs Against Trichomonas Vaginalis

Overview

Journal Parasitol Res

Specialty Parasitology

Date 2022 Jul 20

PMID 35857093

Authors

Mirna Samara Die Alves

Angela Sena-Lopes

Raquel Nascimento das Neves

Angela Maria Casaril

Micaela Domingues

Paloma Taborda Birmann

Emerson Teixeira da Silva

Marcus Vinicius Nora de Souza

Lucielli Savegnago

Sibele Borsuk

Affiliations

Soon will be listed here.

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 IC 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 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 encouraging further studies of this compound as a trichomonacidal agent.

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