Antibacterial Activity of Ebselen

Abstract

Ebselen is a low-molecular-weight organoselenium compound that has been broadly studied for its antioxidant, anti-inflammatory, and cytoprotective properties. These advantageous properties were initially associated with mimicking the activity of selenoprotein glutathione peroxidase, but the biomedical impact of this compound appear to be far more complex. Ebselen serves as a substrate or inhibitor with multiple protein/enzyme targets, whereas inhibition typically originates from the covalent modification of cysteine residues by opening the benzisoselenazolone ring and S–Se bond formation. The inhibition of enzymes of various classes and origins has been associated with substantial antimicrobial potential among other activities. In this contribution, we summarize the current state of the art regarding the antibacterial activity of ebselen. This activity, alone and in combination with commercial pharmaceuticals, against pathogens, including those resistant to drugs, is presented, together with the molecular mechanism behind the reactivity. The specific inactivation of thioredoxin reductase, bacterial toxins, and other resistance factors is considered to have certain therapeutic implications. Synergistic action and sensitization to common antibiotics assisted with the use of ebselen appear to be promising directions in the treatment of persistent infections.

Exploring Immune Redox Modulation in Bacterial Infections: Insights into Thioredoxin-Mediated Interactions and Implications for Understanding Host–Pathogen Dynamics

“…Ebselen, characterized as a seleno-organic compound, demonstrates effective antimicrobial properties against Gram-positive bacteria, notably MRSA, Streptococcus, and Enterococcus, as well as the Gram-negative bacterium H. pylori [20,157]. In various mouse infection models, ebselen demonstrated effectiveness against S. aureus, S. pneumoniae, and C. difficile [158][159][160]. Continuing this line of research, Chen et al synthesized and explored a series of gold (I) selenium N-heterocyclic carbene complexes and found two derivatives with remarkable antibacterial efficacy against multidrug-resistant bacteria.…”

Improving the treatment of bacterial infections caused by multidrug-resistant bacteria through drug repositioning

“…Ebselen is an organoselenium compound studied for its antioxidant, anti-inflammatory, and cytoprotective properties ( Maslanka and Mucha, 2023 ). This molecule displayed high antibacterial activity against strains of Gram-positive bacteria, including S. aureus resistant to methicillin, vancomycin, and linezolid.…”

“…Additionally, it also increased survival in cases of sepsis in animal models. Ebselen also demonstrated activity against strains of vancomycin-resistant enterococci (VRE) and streptococci ( Younis et al, 2015 ; Maslanka and Mucha, 2023 ). Ebselen also inhibited the production of toxins, α-hemolysin, and Panton-Valentine leukocidin, important virulence factors in the pathogenesis of S. aureus .…”

“…When used topically, ebselen reduced the level of pro-inflammatory cytokines in skin infections caused by strains of Staphylococcus . It also showed synergistic activity in combination with many antibiotics, linezolid, clindamycin, vancomycin, chloramphenicol, erythromycin, rifampicin, and gentamicin ( Maslanka and Mucha, 2023 ). The combination of ebselen with isoniazid could also bring good therapeutic effects also against antituberculosis drug-resistant strains of M. tuberculosis ( Padiadpu et al, 2016 ; Sharma et al, 2023 ).…”

Latest Review Papers in Molecular Microbiology

“…Máslanka and Mucha present an alternative to established antibiotics: the organoselenium compound ebselen [ 6 ]. Besides its antioxidative, anti-inflammatory, and cytoprotective activities, ebselen has antibacterial properties, which are discussed with respect to the current state of research, molecular mechanism of antimicrobial activity, and therapeutic implications.…”