β-Nitrostyrene derivatives as broad range potential antifungal agents targeting fungal cell wall

Eur J Med Chem. 2022 Jul 16;240:114609. doi: 10.1016/j.ejmech.2022.114609. Online ahead of print.ABSTRACTThe prevalence of multidrug resistance has been increasingly witnessed during the past few decades. Resistance of human pathogenic fungi against the currently available antifungal agents has increased the frequency of fungal infections and associated mortality rates. The discovery of novel lead antifungal agents is important to challenge multidrug resistance. The present study examined the antifungal potential of chemically synthesized β-Nitrostyrene derivatives. Among the eight β-Nitrostyrene derivatives used in this study, SS45, SS46 and SS47 showed strong antifungal potential. The results show that β-Nitrostyrene derivatives inhibited the growth of different species of human pathogenic Candida, particularly the highly prevalent C. albicans, C. glabrata and the emerging pathogenic C. auris species. Moreover, β-Nitrostyrene derivatives also show strong antifungal activities against drug-resistant clinical isolates and drug transporter overexpressing fungal species. The drug susceptibility assays revealed that β-Nitrostyrene derivatives are fungicidal and show the synergy of action when combined with antifungal drugs caspofungin and fluconazole. The transcriptomic study performed on C. albicans in the presence of β-Nitrostyrene derivatives revealed the differential expression of genes related to cell wall metabolism. Mechanistically, β-Nitrostyrene derivatives impac...
Source: European Journal of Medicinal Chemistry - Category: Chemistry Authors: Source Type: research