Please use this identifier to cite or link to this item: doi:10.22028/D291-27491
Title: Selenazolinium Salts as "Small Molecule Catalysts" with High Potency against ESKAPE Bacterial Pathogens
Author(s): Witek, Karolina
Nasim, Jawad
Bischoff, Markus
Gaupp, Rosmarie
Arsenyan, Pavel
Vasiljeva, Jelena
Marć, Małgorzata Anna
Olejarz, Agnieszka
Latacz, Gniewomir
Kieć-Kononowicz, Katarzyna
Handzlik, Jadwiga
Jacob, Claus
Language: English
Title: Molecules
Volume: 22
Issue: 12
Publisher/Platform: MDPI
Year of Publication: 2017
Free key words: selenazolinium salts
ebselen
DDC notations: 540 Chemistry
Publikation type: Journal Article
Abstract: In view of the pressing need to identify new antibacterial agents able to combat multidrug-resistant bacteria, we investigated a series of fused selenazolinium derivatives (1–8) regarding their in vitro antimicrobial activities against 25 ESKAPE-pathogen strains. Ebselen was used as reference compound. Most of the selenocompounds demonstrated an excellent in vitro activity against all S. aureus strains, with activities comparable to or even exceeding the one of ebselen. In contrast to ebselen, some selenazolinium derivatives (1, 3, and 7) even displayed significant actions against all Gram-negative pathogens tested. The 3-bromo-2-(1-hydroxy-1-methylethyl)[1,2]selenazolo[2,3-a]pyridinium chloride (1) was particularly active (minimum inhibitory concentrations, MICs: 0.31–1.24 µg/mL for MRSA, and 0.31–2.48 µg/mL for Gram-negative bacteria) and devoid of any significant mutagenicity in the Ames assay. Our preliminary mechanistic studies in cell culture indicated that their mode of action is likely to be associated with an alteration of intracellular levels of glutathione and cysteine thiols of different proteins in the bacterial cells, hence supporting the idea that such compounds interact with the intracellular thiolstat. This alteration of pivotal cysteine residues is most likely the result of a direct or catalytic oxidative modification of such residues by the highly reactive selenium species (RSeS) employed.
DOI of the first publication: 10.3390/molecules22122174
Link to this record: urn:nbn:de:bsz:291--ds-274912
hdl:20.500.11880/28599
http://dx.doi.org/10.22028/D291-27491
ISSN: 1420-3049
Date of registration: 17-Jan-2020
Faculty: NT - Naturwissenschaftlich- Technische Fakultät
Department: NT - Pharmazie
Collections:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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