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 ∼ 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 ∼ 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.

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VII) are prepared by ring opening of the crystalline key intermediate (II) in the presence of potassium carbonate. The target compounds possess a chiral center at the C-2 atom and are obtained as N-1, N-2, and N-3 regioisomers and racemic mixtures. Compounds (IIIe), (IVa), and (VIIb) reveal potent antifungal activity. Molecular docking studies provide a better insight into the binding of benzotriazoles within the active site of MTCYP51. -(PATEL, P. D.; PATEL, M. R.; KOCSIS, B.; KOCSIS, E.; GRAHAM, S. M.; WARREN, A. R.; NICHOLSON, S. M.; BILLACK, B.; FRONCZEK, F. R.; TALELE*, T. T.; Eur.