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 |
| |
| Authors: | Natalie N Orie Andrew R Warren Jovana Basaric Cesar Lau‐Cam Magdalena Pi?tka‐Ottlik Jacek M?ochowski Blase Billack |
| |
| Institution: | 1. Department of Pharmaceutical Sciences, St. John's University, Jamaica, NY, USA;2. Division of Organic and Pharmaceutical Technology, Faculty of Chemistry, Wroc?aw University of Technology, Wroc?aw, Poland;3. Department of Organic Chemistry, Faculty of Chemistry, Wroc?aw University of Technology, Wroc?aw, Poland |
| |
| Abstract: | 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 (IC50 ～ 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 (IC50 ～ 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. |
| |
| Keywords: | antifungal activity Candida albicans ebselen ebselen analogs fluconazole‐resistant organoselenium compound organosulfur compound Pma1p plasma membrane H+‐ATPase |
|
|
