Potential of synthetic endoperoxides against Trichomonas vaginalis in vitro

Parasitol Int. 2017 Oct;66(5):619-621. doi: 10.1016/j.parint.2017.05.008. Epub 2017 May 29.

Abstract

Metronidazole is well known for medicine against Trichomonas vaginalis infection, but it has side effects though it is effective, and especially because reports of metronidazole-tolerant species are increasing, the development of new medicine is being required. Here, we noticed the killing effects of endoperoxide compounds, N-89 and N-251 as new antimalarial drug candidates, on T. vaginalis and searched the possibility of development of new medicine. We added each of metronidazole, artemisinin, and two of new endoperoxides (N-89 and N-251) to metronidazole-resistant and -sensitive species and compared its anti-trichomonal efficacy. For metronidazole, IC50 value, 50% of killing concentration for T. vaginalis, was very low for metronidazole-sensitive isolates (11.7 to 22.8μM), but was high for metronidazole-resistant ones (182.9 to 730.4μM). The IC50 values of N-89 and N-251 were 41.0 to 60.0μM, and 82.0 to 300.0μM for metronidazole-sensitive and -resistant isolates, respectively. In conclusion, we found the endoperoxides, N-89 and N-251, have anti-trichomonal effect against metronidazole-resistant T. vaginalis as well as metronidazole-sensitive ones. These results indicate that the anti-trichomonal effects for our endoperoxides are equivalent or better in metronidazole-resistant T. vaginalis in comparison to metronidazole.

Keywords: 1,2,6,7-tetraoxaspiro[7.11]nonadecane (N-89); 6-(1,2,6,7-Tetraoxaspiro[7.11]nonadec-4-yl)hexan-1-ol (N-251); Anti-trichomonal activity; Endoperoxides; Metronidazole-resistant isolate; Trichomonas vaginalis.

MeSH terms

  • Antiprotozoal Agents / pharmacology*
  • Artemisinins / pharmacology
  • Drug Resistance
  • Heterocyclic Compounds, 2-Ring / chemical synthesis
  • Heterocyclic Compounds, 2-Ring / pharmacology*
  • Inhibitory Concentration 50
  • Metronidazole / pharmacology
  • Spiro Compounds / chemical synthesis
  • Spiro Compounds / pharmacology*
  • Tetraoxanes / chemical synthesis
  • Tetraoxanes / pharmacology*
  • Trichomonas vaginalis / drug effects*

Substances

  • 1,2,6,7-tetraoxaspiro(7.11)nonadecane
  • 6-(1,2,6,7-tetraoxaspiro(7.11)nonadec-4-yl)hexan-1-ol
  • Antiprotozoal Agents
  • Artemisinins
  • Heterocyclic Compounds, 2-Ring
  • Spiro Compounds
  • Tetraoxanes
  • Metronidazole
  • artemisinin