Efeito do Ebselen sobre Candida spp.: avaliação in vitro da sensibilidade de células planctônicas e biofilmes, com proposta in silico do mecanismo de ação

Abstract

Infections caused by antifungal-resistant Candida spp. strains have been increasing, and the organoselenium compound Ebselen has emerged as a potential antimicrobial agent. The aim of this study was to evaluate the action of Ebselen on planktonic growth and biofilm formation of Candida species, as well as to investigate a new mechanism of action through molecular docking. Antifungal susceptibility was determined according to CLSI recommendations using antifungals alone and in combination with Ebselen at subinhibitory concentrations (MIC/2, MIC/4, and MIC/8). The effect of the combination on Candida spp. biofilm was evaluated by quantification of biomass and metabolic activity. MIC values for Ebselen ranged from 8 – 0.5 µg/mL (GM = 3.7); for FLC from 128 – 0.5 µg/mL (GM = 35.86); for ITZ from 32 – 0.063 µg/mL (GM = 8.7); for AMB from 0.5 – 0.062 µg/mL (GM = 0.133); and for MCF from 0.125 – 0.5 µg/mL (GM = 0.3). A 100% synergism was observed when antifungals were combined with subinhibitory concentrations (MIC/8) of Ebselen, resulting in reduced mean MIC values for FLC (GM = 1.21), ITZ (GM = 1.21), AMB (GM = 0.015), and MCF (GM = 0.015). Regarding the effect on biofilm, the best interaction was observed in combination with amphotericin and micafungin. Molecular docking revealed a high affinity of Ebselen for Thymidylate kinase, suggesting that its mechanism of action involves interference with DNA synthesis. In summary, Ebselen showed antifungal activity against Candida spp., enhancing the action of antifungals. These findings reinforce the potential of Ebselen as a therapeutic adjuvant in the management of antifungal resistance.