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

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

Volume: 14 Issue: 8

Author(s): Jana Rendekova, Danusa Vlasakova, Pavel Arsenyan*, Jelena Vasiljeva, Muhammad Jawad Nasim, Karolina Witek, Enrique Dominguez-Alvarez, Ewa Zeslawska, Dominika Manikova, Waldemar Tejchman, Rahman Shah Zaib Saleem, Ken Rory, Jadwiga Handzlik and Miroslav Chovanec*

Affiliation:

• Department of Medicinal Chemistry, Latvian Institute of Organic Synthesis, Riga,Latvia

• Department of Genetics, Cancer Research Institute, Biomedical Research Center of Slovak Academy of Science, Bratislava,Slovakia

Keywords: Antimicrobial activity, charge density, chemogenetic screening, DNA damage, reactive selenium species, redox modulation, 77Se NMR, selenazolinium salts.

Abstract: 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.

Cite this article as:

Rendekova Jana, Vlasakova Danusa, Arsenyan Pavel *, Vasiljeva Jelena, Nasim Jawad Muhammad , Witek Karolina, Dominguez-Alvarez Enrique, Zeslawska Ewa, Manikova Dominika, Tejchman Waldemar , Zaib Saleem Shah Rahman , Rory Ken, Handzlik Jadwiga and Chovanec Miroslav *, The Selenium-Nitrogen Bond as Basis for Reactive Selenium Species with Pronounced Antimicrobial Activity, Current Organic Synthesis 2017; 14 (8) . https://dx.doi.org/10.2174/1570179414666170525104735