Real-Time Imaging of the Azole Class of Antifungal Drugs in Live Candida Cells

Raphael I. Benhamou, Maayan Bibi, Kfir B. Steinbuch, Hamutal Engel, Maayan Levin, Yael Roichman, Judith Berman*, Micha Fridman

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

51 Scopus citations


Azoles are the most commonly used class of antifungal drugs, yet where they localize within fungal cells and how they are imported remain poorly understood. Azole antifungals target lanosterol 14α-demethylase, a cytochrome P450, encoded by ERG11 in Candida albicans, the most prevalent fungal pathogen. We report the synthesis of fluorescent probes that permit visualization of antifungal azoles within live cells. Probe 1 is a dansyl dye-conjugated azole, and probe 2 is a Cy5-conjugated azole. Docking computations indicated that each of the probes can occupy the active site of the target cytochrome P450. Like the azole drug fluconazole, probe 1 is not effective against a mutant that lacks the target cytochrome P450. In contrast, the azole drug ketoconazole and probe 2 retained some antifungal activity against mutants lacking the target cytochrome P450, implying that both act against more than one target. Both fluorescent azole probes colocalized with the mitochondria, as determined by fluorescence microscopy with MitoTracker dye. Thus, these fluorescent probes are useful molecular tools that can lead to detailed information about the activity and localization of the important azole class of antifungal drugs.

Original languageAmerican English
Pages (from-to)1769-1777
Number of pages9
JournalACS Chemical Biology
Issue number7
StatePublished - 21 Jul 2017
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2017 American Chemical Society.


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