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Pyridine Derivatives—A New Class of Compounds That Are Toxic to E. coli K12, R2–R4 Strains

A preliminary study of 2-amino-4-aryl-3,5-dicarbonitrile-6-thiopyridines as new potential antimicrobial drugs was performed. Special emphasis was placed on the selection of the structure of target pyridine derivatives with the highest biological activity against different types of Gram-stained bacte...

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Autores principales: Koszelewski, Dominik, Ostaszewski, Ryszard, Śmigielski, Paweł, Hrunyk, Anastasiia, Kramkowski, Karol, Laskowski, Łukasz, Laskowska, Magdalena, Lizut, Rafał, Szymczak, Mateusz, Michalski, Jacek, Gawin, Kamil, Kowalczyk, Paweł
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8467192/
https://www.ncbi.nlm.nih.gov/pubmed/34576625
http://dx.doi.org/10.3390/ma14185401
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author Koszelewski, Dominik
Ostaszewski, Ryszard
Śmigielski, Paweł
Hrunyk, Anastasiia
Kramkowski, Karol
Laskowski, Łukasz
Laskowska, Magdalena
Lizut, Rafał
Szymczak, Mateusz
Michalski, Jacek
Gawin, Kamil
Kowalczyk, Paweł
author_facet Koszelewski, Dominik
Ostaszewski, Ryszard
Śmigielski, Paweł
Hrunyk, Anastasiia
Kramkowski, Karol
Laskowski, Łukasz
Laskowska, Magdalena
Lizut, Rafał
Szymczak, Mateusz
Michalski, Jacek
Gawin, Kamil
Kowalczyk, Paweł
author_sort Koszelewski, Dominik
collection PubMed
description A preliminary study of 2-amino-4-aryl-3,5-dicarbonitrile-6-thiopyridines as new potential antimicrobial drugs was performed. Special emphasis was placed on the selection of the structure of target pyridine derivatives with the highest biological activity against different types of Gram-stained bacteria by lipopolysaccharide (LPS). Herein, Escherichia coli model strains K12 (without LPS in its structure) and R2–R4 (with different lengths of LPS in its structure) were used. Studied target compounds were provided with yields ranging from 53% to 91% by the lipase-catalyzed one pot multicomponent reaction of various aromatic aldehydes with malononitrile, and thiols. The presented work showed that the antibacterial activity of the studied pyridines depends on their structure and affects the LPS of bacteria. Moreover, the influence of the pyridines on bacteria possessing smooth and rough LPS and oxidative damage to plasmid DNA caused by investigated compounds was indicated. Additionally, the modification of the bacterial DNA with the tested compounds was performed to detect new potential oxidative damages, which are recognized by the Fpg protein. The obtained damage modification values of the analyzed compounds were compared with the modifications after antibiotics were used in this type of research. The presented studies demonstrate that 2-amino-4-aryl-3,5-dicarbonitrile-6-thiopyridines can be used as substitutes for known antibiotics. The observed results are especially important in the case of the increasing resistance of bacteria to various drugs and antibiotics.
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spelling pubmed-84671922021-09-27 Pyridine Derivatives—A New Class of Compounds That Are Toxic to E. coli K12, R2–R4 Strains Koszelewski, Dominik Ostaszewski, Ryszard Śmigielski, Paweł Hrunyk, Anastasiia Kramkowski, Karol Laskowski, Łukasz Laskowska, Magdalena Lizut, Rafał Szymczak, Mateusz Michalski, Jacek Gawin, Kamil Kowalczyk, Paweł Materials (Basel) Article A preliminary study of 2-amino-4-aryl-3,5-dicarbonitrile-6-thiopyridines as new potential antimicrobial drugs was performed. Special emphasis was placed on the selection of the structure of target pyridine derivatives with the highest biological activity against different types of Gram-stained bacteria by lipopolysaccharide (LPS). Herein, Escherichia coli model strains K12 (without LPS in its structure) and R2–R4 (with different lengths of LPS in its structure) were used. Studied target compounds were provided with yields ranging from 53% to 91% by the lipase-catalyzed one pot multicomponent reaction of various aromatic aldehydes with malononitrile, and thiols. The presented work showed that the antibacterial activity of the studied pyridines depends on their structure and affects the LPS of bacteria. Moreover, the influence of the pyridines on bacteria possessing smooth and rough LPS and oxidative damage to plasmid DNA caused by investigated compounds was indicated. Additionally, the modification of the bacterial DNA with the tested compounds was performed to detect new potential oxidative damages, which are recognized by the Fpg protein. The obtained damage modification values of the analyzed compounds were compared with the modifications after antibiotics were used in this type of research. The presented studies demonstrate that 2-amino-4-aryl-3,5-dicarbonitrile-6-thiopyridines can be used as substitutes for known antibiotics. The observed results are especially important in the case of the increasing resistance of bacteria to various drugs and antibiotics. MDPI 2021-09-18 /pmc/articles/PMC8467192/ /pubmed/34576625 http://dx.doi.org/10.3390/ma14185401 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Koszelewski, Dominik
Ostaszewski, Ryszard
Śmigielski, Paweł
Hrunyk, Anastasiia
Kramkowski, Karol
Laskowski, Łukasz
Laskowska, Magdalena
Lizut, Rafał
Szymczak, Mateusz
Michalski, Jacek
Gawin, Kamil
Kowalczyk, Paweł
Pyridine Derivatives—A New Class of Compounds That Are Toxic to E. coli K12, R2–R4 Strains
title Pyridine Derivatives—A New Class of Compounds That Are Toxic to E. coli K12, R2–R4 Strains
title_full Pyridine Derivatives—A New Class of Compounds That Are Toxic to E. coli K12, R2–R4 Strains
title_fullStr Pyridine Derivatives—A New Class of Compounds That Are Toxic to E. coli K12, R2–R4 Strains
title_full_unstemmed Pyridine Derivatives—A New Class of Compounds That Are Toxic to E. coli K12, R2–R4 Strains
title_short Pyridine Derivatives—A New Class of Compounds That Are Toxic to E. coli K12, R2–R4 Strains
title_sort pyridine derivatives—a new class of compounds that are toxic to e. coli k12, r2–r4 strains
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8467192/
https://www.ncbi.nlm.nih.gov/pubmed/34576625
http://dx.doi.org/10.3390/ma14185401
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