[:pb]Antiparasitic activity of furanyl N-acylhydrazone derivatives against Trichomonas vaginalis: in vitro and in silico analyses[:]

[:pb]Authors: Alves, M. S. D. ; Das Neves, R. N. ; Sena-Lopes, Â. ; Domingues, M. ; Casaril, A. M. ; Segatto, N. V. ; Nogueira, T. C. M. ; De Souza, M. V. Nora ; Savegnago, L.; Seixas, F. K. ; Collares, T. ; Borsuk, S.
Source: Parasites & Vectors, v. 13, p. 59-72, 2020
Publisher: Springer


Background: Trichomonas vaginalis is the causative agent of trichomoniasis, which is one of the most common sexually transmitted diseases worldwide. Trichomoniasis has a high incidence and prevalence and is associated with serious complications such as HIV transmission and acquisition, pelvic infammatory disease and preterm birth. Although trichomoniasis is treated with oral metronidazole (MTZ), the number of strains resistant to this drug is increasing (2.5–9.6%), leading to treatment failure. Therefore, there is an urgent need to fnd alternative drugs to combat this disease.
Methods: Herein, we report the in vitro and in silico analysis of 12 furanyl N-acylhydrazone derivatives (PFUR 4, a-k) against Trichomonas vaginalis. Trichomonas vaginalis ATCC 30236 isolate was treated with seven concentrations of these compounds to determine the minimum inhibitory concentration (MIC) and 50% inhibitory concentration (IC50). In addition, compounds that displayed anti-T. vaginalis activity were analyzed using thiobarbituric acid reactive substances (TBARS) assay and molecular docking. Cytotoxicity analysis was also performed in CHO-K1 cells.
Results: The compounds PFUR 4a and 4b, at 6.25 µM, induced complete parasite death after 24 h of exposure with
IC50 of 1.69 µM and 1.98 µM, respectively. The results showed that lipid peroxidation is not involved in parasite death. Molecular docking studies predicted strong interactions of PFUR 4a and 4b with T. vaginalis enzymes, purine nucleoside phosphorylase, and lactate dehydrogenase, while only PFUR 4b interacted in silico with thioredoxin reductase and methionine gamma-lyase. PFUR 4a and 4b led to a growth inhibition (<20%) in CHO-K1 cells that was comparable to the drug of choice, with a promising selectivity index (>7.4).
Conclusions: Our results showed that PFUR 4a and 4b are promising molecules that can be used for the development of new trichomonacidal agents for T. vaginalis

Keywords: antiparasitic, lipid peroxidation, molecular docking, trichomoniasis, trichomonacidal

Document Type: Research Article

DOI: 10.1186/s13071-020-3923-8

Publication date: 11 de fevereiro de 2020[:]

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