Synergistic effect of compounds directed to triosephosphate isomerase, a combination to develop drug against trichomoniasis

Arch Pharm (Weinheim). 2022 Jun;355(6):e2200046. doi: 10.1002/ardp.202200046. Epub 2022 Mar 25.

Abstract

The development of new drugs is continuous in the world; currently, saving resources (both economic ones and time) and preventing secondary effects have become a necessity for drug developers. Trichomoniasis is the most common nonviral sexually transmitted infection affecting more than 270 million people around the world. In our research group, we focussed on developing a selective and more effective drug against Trichomonas vaginalis, and we previously reported on a compound, called A4, which had a trichomonacidal effect. Later, we determined another compound, called D4, which also had a trichomonacidal effect together with favorable toxicity results. Both A4 and D4 are directed at the enzyme triosephosphate isomerase. Thus, we made combinations between the two compounds, in which we determined a synergistic effect against T. vaginalis, determining the IC50 and the toxicity of the best relationship to obtain the trichomonacidal effect. With these results, we can propose a combination of compounds that represents a promising alternative for the development of a new therapeutic strategy against trichomoniasis.

Keywords: Trichomonas vaginalis; docking; synergistic effect; triosephosphate isomerase.

MeSH terms

  • Humans
  • Sexually Transmitted Diseases* / complications
  • Sexually Transmitted Diseases* / drug therapy
  • Structure-Activity Relationship
  • Trichomonas Infections* / complications
  • Trichomonas Infections* / drug therapy
  • Trichomonas vaginalis*
  • Triose-Phosphate Isomerase / pharmacology

Substances

  • Triose-Phosphate Isomerase