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

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 (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.

Identification of Antifungal H + -ATPase Inhibitors with Effect on Plasma Membrane Potential

“…The IC 50 of ebselen for C. albicans was found to be 11 μM, in agreement with the previously reported value of 14 μM (18). …”

Reaction of bis[(2-chlorocarbonyl)phenyl] Diselenide with Phenols, Aminophenols, and Other Amines towards Diphenyl Diselenides with Antimicrobial and Antiviral Properties

“…The tremendous efforts in this area has led to the identification of many bioactive structures [ 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 ]. Several enzymes, among them thioredoxin reductase [ 36 , 48 ], bacterial urease [ 49 ], and plasma membrane H+-ATPase [ 50 , 51 , 52 ], were suggested as targets for organoselenium compounds with antimicrobial properties. Furthermore, it has been reported that the antiviral effects of organoselenium compounds might be related to the inhibition of hepatitis C virus NS3 helicase [ 28 ], HIV-1 capsid dimerization [ 29 ], and nucleocapsid protein 7 [ 30 ].…”

Avaliação Do Consumo Alimentar E Peso Corporal Em Camundongos Swiss Machos Tratados Com Extrato Metanólico De Planta Medicinal

“…Na literatura a vários relatos de albuminas vegetais com atividade antifúngica (Cândido et al, 2011;Ribeiro et al, 2012). (Kongstad et al, 2015;Orie et al, 2017). Devido a sua grande relevância, a H + -ATPase surge como um alvo para a ação de novos agentes antifúngicos (Kongstad et al, 2015;Orie et al, 2017).…”