Synthesis, antifungal activity of caffeic acid derivative esters, and their synergism with fluconazole and nystatin against Candida spp.

- Caffeic acid and 8 of its derivative esters were tested for their activity against Candida spp.
- Propyl caffeate (C3) was the most active compound against reference strain and clinical isolates.
- When combined, C3 markedly reduced the MIC of fluconazole and nystatin up to 64-fold.
- C3 showed low toxicity against oral keratinocytes and high selectivity for yeast cells.
- Further research should focus on its combined therapy to treat C. albicans-related infections.

We tested the antifungal potential of caffeic acid and 8 of its derivative esters against Candidaalbicans ATCC 90028 and 9 clinical isolatesand carried out a synergism assay with fluconazole and nystatin. Propyl caffeate (C3) showed the best antifungal activity against the tested strains. When in combination, C3 markedly reduced the MIC of fluconazole and nystatin with synergistic effect up to 64-fold. Finally, C3 showed a high IC50 value and selective indexagainst oral keratinocytes, demonstrating low toxicity against this cell type and selectivity for yeast cells. Further research should confirm its antifungal potential for development of combined therapy to treat C. albicans infections.