Selenazolinium Salts as “Small Molecule Catalysts” with High Potency against ESKAPE Bacterial Pathogens
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 compou...
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MDPI AG
2017-12-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/22/12/2174 |
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| author | Karolina Witek Muhammad Jawad Nasim Markus Bischoff Rosmarie Gaupp Pavel Arsenyan Jelena Vasiljeva Małgorzata Anna Marć Agnieszka Olejarz Gniewomir Latacz Katarzyna Kieć-Kononowicz Jadwiga Handzlik Claus Jacob |
| author_facet | Karolina Witek Muhammad Jawad Nasim Markus Bischoff Rosmarie Gaupp Pavel Arsenyan Jelena Vasiljeva Małgorzata Anna Marć Agnieszka Olejarz Gniewomir Latacz Katarzyna Kieć-Kononowicz Jadwiga Handzlik Claus Jacob |
| author_sort | Karolina Witek |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-20T21:05:30Z |
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| id | doaj.art-0b734f77933243c9919a1b19baf89157 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-20T21:05:30Z |
| publishDate | 2017-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-0b734f77933243c9919a1b19baf891572022-12-21T19:26:36ZengMDPI AGMolecules1420-30492017-12-012212217410.3390/molecules22122174molecules22122174Selenazolinium Salts as “Small Molecule Catalysts” with High Potency against ESKAPE Bacterial PathogensKarolina Witek0Muhammad Jawad Nasim1Markus Bischoff2Rosmarie Gaupp3Pavel Arsenyan4Jelena Vasiljeva5Małgorzata Anna Marć6Agnieszka Olejarz7Gniewomir Latacz8Katarzyna Kieć-Kononowicz9Jadwiga Handzlik10Claus Jacob11Department of Technology and Biotechnology of Drugs, Faculty of Pharmacy, Jagiellonian University, Medical College, ul. Medyczna 9, 30-688 Cracow, PolandDepartment of Technology and Biotechnology of Drugs, Faculty of Pharmacy, Jagiellonian University, Medical College, ul. Medyczna 9, 30-688 Cracow, PolandInstitute of Medical Microbiology and Hygiene, Saarland University, D-66421 Homburg, GermanyInstitute of Medical Microbiology and Hygiene, Saarland University, D-66421 Homburg, GermanyDepartment of Medicinal Chemistry, Latvian Institute of Organic Synthesis, Aizkraukles 21, LV-1006 Riga, LatviaDepartment of Medicinal Chemistry, Latvian Institute of Organic Synthesis, Aizkraukles 21, LV-1006 Riga, LatviaDepartment of Technology and Biotechnology of Drugs, Faculty of Pharmacy, Jagiellonian University, Medical College, ul. Medyczna 9, 30-688 Cracow, PolandDepartment of Technology and Biotechnology of Drugs, Faculty of Pharmacy, Jagiellonian University, Medical College, ul. Medyczna 9, 30-688 Cracow, PolandDepartment of Technology and Biotechnology of Drugs, Faculty of Pharmacy, Jagiellonian University, Medical College, ul. Medyczna 9, 30-688 Cracow, PolandDepartment of Technology and Biotechnology of Drugs, Faculty of Pharmacy, Jagiellonian University, Medical College, ul. Medyczna 9, 30-688 Cracow, PolandDepartment of Technology and Biotechnology of Drugs, Faculty of Pharmacy, Jagiellonian University, Medical College, ul. Medyczna 9, 30-688 Cracow, PolandBioorganic Chemistry, School of Pharmacy, University of Saarland, Campus B2.1, D-66123 Saarbruecken, GermanyIn 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.https://www.mdpi.com/1420-3049/22/12/2174selenazolinium saltsebselenRSeSmultidrug resistanceMRSAESKAPE pathogensantibacterial agents |
| spellingShingle | Karolina Witek Muhammad Jawad Nasim Markus Bischoff Rosmarie Gaupp Pavel Arsenyan Jelena Vasiljeva Małgorzata Anna Marć Agnieszka Olejarz Gniewomir Latacz Katarzyna Kieć-Kononowicz Jadwiga Handzlik Claus Jacob Selenazolinium Salts as “Small Molecule Catalysts” with High Potency against ESKAPE Bacterial Pathogens Molecules selenazolinium salts ebselen RSeS multidrug resistance MRSA ESKAPE pathogens antibacterial agents |
| title | Selenazolinium Salts as “Small Molecule Catalysts” with High Potency against ESKAPE Bacterial Pathogens |
| title_full | Selenazolinium Salts as “Small Molecule Catalysts” with High Potency against ESKAPE Bacterial Pathogens |
| title_fullStr | Selenazolinium Salts as “Small Molecule Catalysts” with High Potency against ESKAPE Bacterial Pathogens |
| title_full_unstemmed | Selenazolinium Salts as “Small Molecule Catalysts” with High Potency against ESKAPE Bacterial Pathogens |
| title_short | Selenazolinium Salts as “Small Molecule Catalysts” with High Potency against ESKAPE Bacterial Pathogens |
| title_sort | selenazolinium salts as small molecule catalysts with high potency against eskape bacterial pathogens |
| topic | selenazolinium salts ebselen RSeS multidrug resistance MRSA ESKAPE pathogens antibacterial agents |
| url | https://www.mdpi.com/1420-3049/22/12/2174 |
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