Candidiasis arises from the proliferation of
Candida species in the human body, especially in individuals with compromised immune systems. Efficient therapeutic management of candidiasis is often hampered by the limited availability of potent antifungal drugs and the emergence of drug-resistant strains. We have
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Candidiasis arises from the proliferation of
Candida species in the human body, especially in individuals with compromised immune systems. Efficient therapeutic management of candidiasis is often hampered by the limited availability of potent antifungal drugs and the emergence of drug-resistant strains. We have previously identified the
N-[(4-sulfamoylphenyl)methyl][1,1′-biphenyl]-4-carboxamide to have fungistatic and fungicidal properties, likely due to the hydrophobic biphenyl–chemical features affecting the structural organization of
Candida spp. cell membrane. Here, we designed and synthesized a novel series of twelve 5-arylfuran-2-carboxamide derivatives bearing a new hydrophobic tail as bioisosteric replacement of the diphenyl fragment. Its antifungal effectiveness against
C. albicans,
C. glabrata, and
C. parapsilosis, including ATCC and clinically isolated strains, was assessed for all compounds. The most active compound was
N-benzyl-5-(3,4-dichlorophenyl)furan-2-carboxamide (
6), with fungistatic and fungicidal effects against
C. glabrata and
C. parapsilosis strains (MIC = 0.062–0.125 and 0.125–0.250 mg/mL, respectively). No synergistic effects were observed when combined with fluconazole. Interestingly, fluorescent microscopy analysis after staining with SYTO 9 and propidium iodide revealed that compound
6 affected the cell membrane integrity in
C. albicans strain 16. Finally, carboxamide
6 exhibited a dose-dependent cytotoxicity on erythrocytes, based on assessing the LDH release.
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