The Selenium-Nitrogen Bond as Basis for Reactive Selenium Species with Pronounced Antimicrobial Activity

Aim and Objective: Selenium (Se) compounds are often associated with good reactivity and selectivity due to specific modifications of thiol groups in peptides, proteins and enzymes. Among them, selenazolinium salts are of particular interest, as they react readily with their thiol targets. This study was undertaken to verify whether this reactivity translates into biological activity against a few selected organisms. Materials and Methods: To screen the activity of selenazolinium salts, we performed nematicidal activity assay using Steinernema feltiae. To determine their impact on microbial proliferation, viability of Escherichia coli and Saccharomyces cerevisiae cells was monitored. For a chemical genetic phenotyping focused on a redox link, 32 redox-related S. cerevisiae mutants were used. DNA double-strand breakage caused by selenazolinium salts was investigated using pulsed-field gel electrophoresis and their physico-chemical properties were assessed using nuclear magnetic resonance (NMR). Results: Some of selenazolinium salts are toxic against S. feltiae at a concentration of 100-500 μM. In E. coli, selenazolium salts display no toxicity at a concentration of 100 μM; however, at a concentration of 500 μM some of them show a statistically relevant toxicity. Similar findings were obtained in wild-type S. cerevisiae cells. Only a few redox-related mutants show higher sensitivity to selenazolinium salts compared to wild-type cells. Selenazolinium salts induce DNA double-strand breaks at moderate doses (10-100 μM). 77Se-NMR shifts reflect some of the trends observed in the biological assays. Conclusion: Our results confirmed that several of selenazolinium salts show a significant biological activity that is executed via an electrophilic attack.