Design, synthesis and evaluation of novel 5-phenylthiophene derivatives as potent fungicidal of Candida albicans and antifungal reagents of fluconazole-resistant fungi

A series of 5-phenylthiophene derivatives with novel structures were designed and synthesized to combat the increasing incidence of susceptible and drug-resistant fungal infections. The antifungal activity of the synthesized compounds was assessed against seven susceptible strains and six fluconazole-resistant strains. It is especially encouraging that compounds 17b and 17f displayed significant antifungal activities against all tested strains. Furthermore, the potent compounds 17b and 17f could prevent the formation of fungi biofilms and 17f displayed satisfactory fungicidal activity. Preliminary mechanistic studies showed that the potent antifungal activity of compound 17f stemmed from inhibition of C. albicans CYP51. In addition, Compounds 17b and 17f were almost nontoxic to mammalian A549, MCF7, and THLE-2 cells. These results strongly suggested that compounds 17b and 17f are promising as novel antifungal drugs. (C) 2021 Elsevier Masson SAS. All rights reserved.

Automated summary

A series of novel 5-phenylthiophene derivatives were designed and synthesized to combat fungal infections, with compounds 17b and 17f showing significant antifungal activities. These compounds not only prevented the formation of fungal biofilms, but also displayed satisfactory fungicidal activity against various strains. Compound 17f exhibited potent antifungal activity by inhibiting C. albicans CYP51, and both 17b and 17f were almost non-toxic to mammalian cells, indicating their promise as novel antifungal drugs.