Novel nucleosides as potential inhibitors of fungal lanosterol 14α-demethylase: an in vitro and in silico study

Abstract

Aim: The global burden of fungal infections has transitioned from a case–specific observation to a major cause of high human mortality. Therefore, novel compounds with innovative methodologies need to be synthesized and evaluated for their antifungal potential to keep pace with the current clinical demands. Results: An efficient synthetic pathway was developed for the synthesis of 21 synthetic novel nucleosides. Two compounds had significant antifungal effect on Aspergillus fumigatus 3007, which was comparable to fluconazole. The experimental data (confocal microscopy, ultrahigh-performance liquid chromatography and flow cytometry) demonstrated the inhibition of fungal lanosterol 14α-demethylase. Conclusion: Owing to the therapeutic relevance of the synthesized nucleosides and simplicity of the procedure, the method may find its potential application for synthesis of antifungal agents.