Discovery of Antifungal Norsesquiterpenoids from a Soil-Derived : Targeting Biofilm Formation and Synergistic Combination with Amphotericin B against Yeast-like Fungi.

Thirty-five norsesquiterpenoids were isolated from the fermentation broth of from the forest soil of Ailaoshan in China. The structures of new compounds (-, -) were elucidated by comprehensive spectroscopic analysis including data from experimental and calculated ECD spectra, as well as Mosher's reagent derivatives method. Norsesquiterpenoids showed different levels of antifungal activity with MIC values ranging from 25 to 200 μg/mL against , , and . The combining isolated norsesquiterpenoids with amphotericin B resulted in a synergistic interaction against test yeast-like fungi with a fractional inhibitory concentration index < 0.5. Compound significantly inhibited biofilm formation and destroyed the preformed biofilm of fungi. Moreover, downregulated the expression of adhesion-related genes , , and to inhibit the adhesion of . Findings from the current study highlight the potential usage of norsesquiterpenoids from soil-derived for antifungal leads discovery.