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

Autor: Alves MSD; Laboratório de Biotecnologia Infecto-parasitária, Centro de Desenvolvimento Tecnológico, Biotecnologia, UFPel, Pelotas, RS, 96010-900, Brazil., das Neves RN; Laboratório de Biotecnologia Infecto-parasitária, Centro de Desenvolvimento Tecnológico, Biotecnologia, UFPel, Pelotas, RS, 96010-900, Brazil., Sena-Lopes Â; Laboratório de Biotecnologia Infecto-parasitária, Centro de Desenvolvimento Tecnológico, Biotecnologia, UFPel, Pelotas, RS, 96010-900, Brazil., Domingues M; Laboratório de Neurobiotecnologia, Centro de Desenvolvimento Tecnológico, Biotecnologia, UFPel, Pelotas, RS, 96010-900, Brazil., Casaril AM; Laboratório de Neurobiotecnologia, Centro de Desenvolvimento Tecnológico, Biotecnologia, UFPel, Pelotas, RS, 96010-900, Brazil., Segatto NV; Laboratório de Biotecnologia do Câncer, Centro de Desenvolvimento Tecnológico, Biotecnologia, UFPel, Pelotas, RS, 96010-900, Brazil., Nogueira TCM; Instituto de Tecnologia em Fármacos-Far-Manguinhos, Fiocruz-Fundação Oswaldo Cruz, Rio de Janeiro, RJ, 21041-250, Brazil., de Souza MVN; Instituto de Tecnologia em Fármacos-Far-Manguinhos, Fiocruz-Fundação Oswaldo Cruz, Rio de Janeiro, RJ, 21041-250, Brazil.; Programa de Pós-Graduação em Química, Instituto de Química, Universidade Federal do Rio de Janeiro, Cidade Universitária, Rio de Janeiro, RJ, 21945-970, Brazil., Savegnago L; Laboratório de Neurobiotecnologia, Centro de Desenvolvimento Tecnológico, Biotecnologia, UFPel, Pelotas, RS, 96010-900, Brazil., Seixas FK; Laboratório de Biotecnologia do Câncer, Centro de Desenvolvimento Tecnológico, Biotecnologia, UFPel, Pelotas, RS, 96010-900, Brazil., Collares T; Laboratório de Biotecnologia do Câncer, Centro de Desenvolvimento Tecnológico, Biotecnologia, UFPel, Pelotas, RS, 96010-900, Brazil., Borsuk S; Laboratório de Biotecnologia Infecto-parasitária, Centro de Desenvolvimento Tecnológico, Biotecnologia, UFPel, Pelotas, RS, 96010-900, Brazil. sibeleborsuk@gmail.com.
Jazyk: angličtina
Zdroj: Parasites & vectors [Parasit Vectors] 2020 Feb 11; Vol. 13 (1), pp. 59. Date of Electronic Publication: 2020 Feb 11.
DOI: 10.1186/s13071-020-3923-8
Abstrakt: 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 inflammatory 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 find 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 (IC 50 ). 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 IC 50 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.
Databáze: MEDLINE
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