Abstract
The scarce antifungal arsenal, changes in the susceptibility profile of fungal agents, and lack of adherence to treatment have contributed to the increase of cases of dermatomycoses. In this context, new antimicrobial substances have gained importance. Chalcones are precursors of the flavonoid family that have multiple biological activities, have high tolerability by humans, and easy synthesis. In this study, we evaluated the in vitro antifungal activity, alone and in combination with conventional antifungal drugs, of the VS02–4′ethyl chalcone-derived compound against dermatophytes and Candida spp. Susceptibility testing was carried out by broth microdilution. Experiments for determination of the target of the compound on the fungal cell, time-kill kinetics, and toxicity tests in Galleria mellonella model were also performed. Combinatory effects were evaluated by the checkerboard method. Results showed high activity of the compound VS02–4′ethyl against dermatophytes (MIC of 7.81–31.25 μg/ml). The compound targeted the cell membrane, and the time-kill test showed the compound continues to exert gradual activity after 5 days on dermatophytes, but no significant activity on Candida. Low toxicity was observed at 250 mg/kg. Excellent results were observed in the combinatory test, where VS02–4′ethyl showed synergistic interactions with itraconazole, fluconazole, terbinafine, and griseofulvin, against all isolates tested. Although further investigation is needed, these results revealed the great potential of chalcone-derived compounds against fungal infections for which treatments are long and laborious.
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Acknowledgements
Authors would like to thank the Laboratory of Microbiology of the São José do Rio Preto School of Medicine (FAMERP) and the Laboratory of Antibiotics and Chemotherapeutics of the São Paulo State University (Unesp), Institute of Biosciences, Humanities and Exact Sciences, São José do Rio Preto, Brazil.
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TML and MTGA the study conception and design. PTC and LOR helped synthesize the compound. TML and BGA performed the literature search and data analysis. TML, THL and MDRM performed the material preparation and data collection. GRC and MRVZK carried out the toxicity test. TML and JPZS wrote the first draft of the manuscript. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
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Maschio-Lima, T., Lemes, T.H., Marques, M.D.R. et al. Synergistic activity between conventional antifungals and chalcone-derived compound against dermatophyte fungi and Candida spp.. Int Microbiol (2024). https://doi.org/10.1007/s10123-024-00541-7
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DOI: https://doi.org/10.1007/s10123-024-00541-7