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In vitro assessment of the growth and plasma membrane H + ‐ATPase inhibitory activity of ebselen and structurally related selenium‐ and sulfur‐containing compounds in Candida albicans
Author(s) -
Orie Natalie N.,
Warren Andrew R.,
Basaric Jovana,
LauCam Cesar,
PiętkaOttlik Magdalena,
Młochowski Jacek,
Billack Blase
Publication year - 2017
Publication title -
journal of biochemical and molecular toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.526
H-Index - 58
eISSN - 1099-0461
pISSN - 1095-6670
DOI - 10.1002/jbt.21892
Subject(s) - ebselen , candida albicans , in vitro , yeast , inhibitory postsynaptic potential , biochemistry , chemistry , minimum inhibitory concentration , membrane , growth inhibition , atpase , strain (injury) , pi , corpus albicans , fluconazole , potency , stereochemistry , enzyme , microbiology and biotechnology , biology , antifungal , glutathione , glutathione peroxidase , anatomy , neuroscience
Ebselen (EB, compound 1) is an investigational organoselenium compound that reduces fungal growth, in part, through inhibition of the fungal plasma membrane H + ‐ATPase (Pma1p). In the present study, the growth inhibitory activity of EB and of five structural analogs was assessed in a fluconazole (FLU)‐resistant strain of Candida albicans (S2). While none of the compounds were more effective than EB at inhibiting fungal growth (IC 50 ∼ 18 μM), two compounds, compounds 5 and 6, were similar in potency. Medium acidification assays performed with S2 yeast cells revealed that compounds 4 and 6, but not compounds 2, 3, or 5, exerted an inhibitory activity comparable to EB (IC 50 ∼ 14 μM). Using a partially purified Pma1p preparation obtained from S2 yeast cells, EB and all the analogs demonstrated a similar inhibitory activity. Taken together, these results indicate that EB analogs are worth exploring further for use as growth inhibitors of FLU‐resistant fungi.