Evaluation of the antifungal and plasma membrane H⁺-ATPase inhibitory action of ebselen and two ebselen analogs in S. cerevisiae cultures

Figures & data

Table 1.  Growth inhibitory effect of ebselen (compound 1) and its analogs on AH109 cells.

Compound	Chemical structure	Chemical name	IC50 (µM)^a
1		2-phenylbenzisoselenazol-3(2H)-one	4.6 ± 0.4
2		2-(3-pyridinyl)-benzisoselenazol-3(2H)-one	18.0 ± 1.0
3		2-phenylbenzisoselenazol-3(2H)-one 1-oxide	2.1 ± 0.4

^aIC₅₀ values are reported as mean ± SEM derived from three independent experiments.

Figure 1.  Effect of compounds 1, 2, and 3 on (A) yeast growth and (B–D) Pma1p activity. Statistical comparisons were against untreated control and found to be significantly different at ^†p < 0.05, ^††p < 0.01, and ^†††p < 0.001.

Table 2.  Inhibition of the yeast plasma membrane H⁺-ATPase pump by ebselen (compound 1) and two of its analogs.

Compound	Chemical formula	Calculated log P^a,b	IC50 (µM)^c
1	C13H9NOSe	1.88	2.5 ± 0.5
2	C12H8N2OSe	1.25	6.7 ± 1.7
3	C13H9NO2Se	1.88	4.0 ± 0.2

^aLog P is the octanol:water partition coefficient.

^bDetermined using the Interactive LogKow Online Program for log P determination available at:http://www.srcinc.com/what-we-do/databaseforms.aspx id = 385 (last accessed May 15, 2009).

^cIC₅₀ values are reported as mean ± SEM derived from three independent experiments.

Figure 2.  Thin layer chromatographic analysis of the products formed by reacting (30 mM) ebselen, (18 mM) compound 2, or (30 mM) compound 3 with (30 mM) l-cysteine. Lane 1, l-cysteine; lane 2, ebselen (dotted circle); lane 3, ebselen overspotted with l-cysteine; lane 4, compound 2 (dotted circle); lane 5, compound 2 overspotted with l-cysteine; lane 6, compound 3 (dotted circle); lane 7, compound 3 overspotted with l-cysteine; lane 8, l-cysteine. Note that lanes 3, 5, and 7 reveal that the l-cysteine spot has disappeared and that new spots (solid circles) with a slower migration rate than compounds 1, 2, and 3, respectively, are observed. l-cysteine was visualized with ninhydrin reagent followed by warming at 70°C in an oven.