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Parasitology Research

, Volume 113, Issue 6, pp 2185–2197 | Cite as

The effect of 3-(biphenyl-4-yl)-3-hydoxyquinuclidine (BPQ-OH) and metronidazole on Trichomonas vaginalis: a comparative study

  • Débora Afonso Silva Rocha
  • Ivone de Andrade Rosa
  • Julio A. Urbina
  • Wanderley de Souza
  • Marlene Benchimol
Original Paper

Abstract

Trichomonas vaginalis causes trichomoniasis in humans, a sexually transmitted disease commonly treated with metronidazole (MTZ), a drug that presents some toxicity, causing undesirable side effects. In addition, an increase in metronidazole-resistant parasites has been reported. Thus, the development of alternative treatment is recommended. To date, the search for antiparasitic drugs has been based on different approaches: identification of active natural products, identification of parasite targets, and the use of available compounds active against other pathogenic microorganisms. Here, we analyzed the in vitro antiproliferative and ultrastructural effects on T. vaginalis of BPQ-OH, a hydroxiquinuclidine derivative that inhibits squalene synthase and is active against several protozoa and fungi. We also compared the effects of BPQ-OH on T. vaginalis and mammalian cells with those of MTZ. We found that BPQ-OH inhibits in vitro proliferation of T. vaginalis, with an IC50 of 46 μM after 24 h. Although this IC50 is 16 times higher than that of MTZ (1.8 μM), BPQ-OH is less toxic for human cell lines than MTZ, with LC50 values of 2,300 and 70 μM, and selective indexes of 50 and 39, respectively. Ultrastructural analyses demonstrated that BPQ-OH induced alterations in T. vaginalis, such as rounded and wrinkled cells, membrane blebbing and intense vacuolization, leading to cell death, whereas MTZ also caused significant changes, including a decrease in hydrogenosomes size and endoflagellar forms. Our observations identify BPQ-OH as a promising leading compound for the development of novel anti-T. vaginalis drugs and highlight the need for further testing this molecule using experimentally infected animals.

Keywords

Trichomonas vaginalis Hydroxiquinuclidine derivative BPQ-OH Metronidazole Ultrastructure Viability 

Notes

Acknowledgments

This work was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Programa de Núcleos de Excelência (PRONEX), Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ) and Associação Universitária Santa Úrsula (AUSU).

Ethical Standards

The experiments comply with the current laws of this country.

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

436_2014_3871_Fig8_ESM.jpg (612 kb)
Figure S1

Morphometric analysis of T. vaginalis (a) and hydrogenosomes (b) area after MTZ treatment. (a) The cell area and the hydrogenosomes number were not affected by MTZ treatment; however, the hydrogenosomes were significantly smaller in MTZ-treated cells (c). (JPEG 612 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Débora Afonso Silva Rocha
    • 1
    • 2
    • 4
  • Ivone de Andrade Rosa
    • 1
    • 2
    • 4
  • Julio A. Urbina
    • 5
    • 6
  • Wanderley de Souza
    • 3
    • 4
    • 5
  • Marlene Benchimol
    • 1
    • 4
  1. 1.Universidade Santa ÚrsulaRio de JaneiroBrazil
  2. 2.Instituto de Biofísica Carlos Chagas FilhoUniversidade Federal do Rio de JaneiroRio de JaneiroBrazil
  3. 3.Laboratório de Ultraestrutura Celular Hertha Meyer, Instituto de Biofísica Carlos Chagas FilhoUniversidade Federal do Rio de JaneiroRio de JaneiroBrazil
  4. 4.Instituto Nacional de Ciência e Tecnologia em Biologia Estrutural e Bioimagens-INBEBUniversidade Federal do Rio de JaneiroRio de JaneiroBrazil
  5. 5.Instituto Nacional de Metrologia, Qualidade e Tecnologia-Inmetro, Duque de CaxiasRio de JaneiroBrazil
  6. 6.Instituto Venezolano de Investigaciones CientificasCaracasVenezuela

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