Synthesis and antifungal evaluation against Candida spp. of the (E)-3-(furan-2-yl)acrylic acid

Paulo César Trindade da Costa1, Thales Luciano Bezerra Santos2, Jaqueline Ferreira Ramos3

  • 1Health Sciences Center, Federal University of Paraiba, Cidade Universitária, João Pessoa, PB, 58051-900, Brazil. paulocesarnutricionista@gmail.com.

Insights

A novel compound, (E)-3-(furan-2-yl)acrylic acid, shows significant antifungal activity against Candida species. It also demonstrated synergistic effects with amphotericin B and reduced Candida albicans virulence factors.

Area of Science:

  • Mycology
  • Medicinal Chemistry

Background:

  • Fungal infections, primarily caused by Candida species like Candida albicans, pose a significant threat to human health.
  • Developing novel antifungal agents is crucial due to increasing drug resistance.

Purpose of the Study:

  • To synthesize and evaluate the antifungal potential of (E)-3-(furan-2-yl)acrylic acid against pathogenic Candida species.
  • To investigate the compound's synergistic effects, impact on Candida albicans morphology and virulence, and its fungistatic properties.

Main Methods:

  • Chemical synthesis of (E)-3-(furan-2-yl)acrylic acid with yield determination.
  • Antifungal susceptibility testing using minimum inhibitory concentration (MIC) assays against four Candida species.
  • Evaluation of synergistic and antagonistic effects in combination with amphotericin B and fluconazole.
  • Microscopic observation of morphological changes in Candida albicans.
  • Growth kinetics analysis to determine the fungistatic profile.
  • Assessment of ergosterol biosynthesis stimulation.

Main Results:

  • High synthesis yield (88%) achieved for (E)-3-(furan-2-yl)acrylic acid.
  • The compound exhibited antifungal activity with MICs ranging from 64 to 512 μg/mL against tested Candida species.
  • Synergistic antifungal effect observed when combined with amphotericin B against Candida albicans and Candida tropicalis.
  • The compound induced morphological alterations in Candida albicans, reducing virulence factors and reproductive structures.
  • Fungistatic activity confirmed through growth kinetics studies.
  • Stimulation of ergosterol biosynthesis in Candida albicans was noted.

Conclusions:

  • (E)-3-(furan-2-yl)acrylic acid is a promising candidate for antifungal drug development.
  • Its synergistic potential with existing antifungals and ability to reduce virulence warrant further investigation.
  • The compound's mechanism may involve modulating ergosterol biosynthesis and inducing cellular stress responses in Candida species.