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Published on: February 14, 2018
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.
Abstract:
Infections of fungal origin are mainly caused by Candida spp. Some species, such as C. albicans, C. glabrata, C. parapsilosis, and C. tropicalis, stand out as promoters of diseases in humans. This study evaluated the synthesis and antifungal effects of (E)-3-(furan-2-yl)acrylic acid. The synthesis of the compound showed a yield of 88%, considered high. The minimum inhibitory concentration of the synthetic compound, amphotericin B, and fluconazole isolated against four Candida species ranged from 64 to 512 μg/mL, 1 to 2 μg/mL, and 32 to 256 μg/mL, respectively. The synergistic effect of the test compound was observed when associated with amphotericin B against C. albicans and C. tropicalis, with no antagonism between the substances against any of the strains tested. The potential drug promoted morphological changes in C. albicans, decreasing the amount of resistance and virulence, and reproduction structures, such as the formation of pseudohyphae, blastoconidia, and chlamydospores. Furthermore, it was also possible to identify the fungistatic profile of the test substance by studying the growth kinetics of C. albicans. Finally, it was observed that the test compound stimulated ergosterol biosynthesis by the yeast, probably by activating microbial resistance responses.
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.
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