Design, synthesis, docking studies and bioactivity evaluation of 1,2,3-triazole eugenol derivatives

Future Med Chem. 2024;16(18):1883-1897. doi: 10.1080/17568919.2024.2385292. Epub 2024 Aug 19.

Abstract

Aim: The design, synthesis, docking studies and evaluation of the in vitro antifungal and cytotoxic properties of eugenol (EUG) containing 1,2,3-triazole derivatives are reported. Most of the derivatives have not been reported.Materials & methods: The EUG derivatives were synthesized, molecular docked and tested for their antifungal activity.Results: The compounds showed potent antifungal activity against Trichophyton rubrum, associated with dermatophytosis. Compounds 2a and 2i exhibited promising results, with 2a being four-times more potent than EUG. The binding mode prediction was similar to itraconazole in the lanosterol-14-α-demethylase wild-type and G73E mutant binding sites. Additionally, the pharmacokinetic profile prediction suggests good gastrointestinal absorption and potential oral administration.Conclusion: Compound 2a is a promising antifungal agent against dermatophytosis caused by T. rubrum.

Keywords: Trichophyton; antifungal activity; dermatophytes; eugenol; triazole compounds.

Plain language summary

[Box: see text].

MeSH terms

  • Antifungal Agents* / chemical synthesis
  • Antifungal Agents* / chemistry
  • Antifungal Agents* / pharmacology
  • Drug Design*
  • Eugenol* / analogs & derivatives
  • Eugenol* / chemical synthesis
  • Eugenol* / chemistry
  • Eugenol* / pharmacology
  • Humans
  • Microbial Sensitivity Tests*
  • Molecular Docking Simulation*
  • Molecular Structure
  • Structure-Activity Relationship
  • Triazoles* / chemical synthesis
  • Triazoles* / chemistry
  • Triazoles* / pharmacology
  • Trichophyton / drug effects

Substances

  • Eugenol
  • Triazoles
  • Antifungal Agents