Diamine derivative anti-Trichomonas vaginalis and anti-Tritrichomonas foetus activities by effect on polyamine metabolism

Biomed Pharmacother. 2017 Nov:95:847-855. doi: 10.1016/j.biopha.2017.09.007. Epub 2017 Sep 10.

Abstract

Human and bovine trichomoniasis are sexually transmitted diseases (STD) caused by Trichomonas vaginalis and Tritrichomonas foetus, respectively. Human trichomoniasis is the most common non-viral STD in the world and bovine trichomoniasis causes significant economic losses to breeders. Considering the significant impact of the infections caused by these protozoa and the treatment failures, the search for new therapeutic alternatives becomes crucial. In this study the effect of diamines and amino alcohols in the in vitro viability of trichomonads was evaluated. Screening demonstrated the high activity of diamine 4 against these protozoa. Although cytotoxicity against HMVII cell line and slight hemolysis were observed in vitro, the compound showed no toxic effect on the Galleria mellonella in vivo model. Importantly, diamine 4 was active against both trichomonads species at 6h and 24h of incubation, and these effects was reverted by putrescine, a polyamine, suggesting competition for the same metabolic pathway. These findings indicate that the mechanism of action of diamine 4 is through the polyamine metabolism, a pathway distinct from that presented by metronidazole, the drug usually used to treat trichomoniasis and to which resistance is widely reported. These data demonstrate the importance of diamines as potential novel candidates as anti-T. vaginalis and anti-T. foetus agents.

Keywords: Anti-trichomonads activity; Diamine derivatives; Polyamine metabolism; Trichomonas vaginalis; Tritrichomonas foetus.

MeSH terms

  • Cell Cycle / drug effects
  • Cell Line
  • Cell Survival / drug effects
  • Diamines / pharmacology*
  • Hemolysis / drug effects
  • Humans
  • Kinetics
  • Microbial Sensitivity Tests
  • Models, Biological
  • Polyamines / metabolism*
  • Reactive Oxygen Species / metabolism
  • Trichomonas vaginalis / drug effects*
  • Trichomonas vaginalis / growth & development
  • Tritrichomonas foetus / drug effects*
  • Tritrichomonas foetus / growth & development

Substances

  • Diamines
  • Polyamines
  • Reactive Oxygen Species