Dehydrozingerone Exhibits Synergistic Antifungal Activities in Combination with Dodecanol against Budding Yeast via the Restriction of Multidrug Resistance

Abstract

Drug resistance in fungal infections has been a more frequent occurrence with the increasing number of immunocompromised patients. In efforts to overcome the problem of fungal drug resistance, we focused on the phenolic compound dehydrozingerone, which is isolated from Zingiber officinale. The effectiveness of this compound on the model yeast Saccharomyces cerevisiae has not been reported. In our study, dehydrozingerone showed a weak antifungal activity against the yeast, but demonstrated a synergistic effect in combination with dodecanol, which typically only restricts cell growth transiently. Efflux of rhodamine 6G through the multidrug efflux pumps was significantly restricted by dehydrozingerone. The transcription level of PDR5, encoding a primary multidrug efflux pump in S. cerevisiae, was enhanced with dodecanol treatment, whereas the level was reduced by dehydrozingerone. These results suggest that dehydrozingerone may be effective for potentiating antifungal activity of other drugs that are expelled from fungi by multidrug transporters like Pdr5p.

Investigation of bioactivities of Taxus chinensis, Taxus cuspidata, and Taxus × media by gas chromatography-mass spectrometry

“…The highest contents of these metabolites were observed in T. media . Among them, dodecanol has an antifungal effect [ 19 ]. Phosphomycin, fumaric acid, caffeic acid, cis -2-hydroxycinnamic acid, 4-hydroxybenzoic acid, and 3,4-dihydroxyphenylacetic acid boast the broad-spectrum antibacterial property.…”

Structure–activity relationships of antifungal phenylpropanoid derivatives and their synergy with n ‐dodecanol and fluconazole

“…Assays were performed as described (Yamawaki et al 2018(Yamawaki et al , 2019. Serial, twofold dilutions of the compounds were prepared in DMF.…”