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

Dominik Koszelewski,Anastasiia Hrunyk,Mateusz Szymczak,Kamil Gawin,Magdalena Laskowska,Paweł Kowalczyk,Ryszard Ostaszewski,Łukasz Laskowski,Jacek Michalski,Rafał Lizut,Paweł Śmigielski,Karol Kramkowski

doi:10.3390/ma14185401

Abstract

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.

Highlights

IntroductionThe pyridine ring system can be found in a number of natural products and in several pharmacologically relevant compounds
Licensee MDPI, Basel, Switzerland.The pyridine ring system can be found in a number of natural products and in several pharmacologically relevant compounds
Since we observed the greatest number of modifications after treatment with the Fpg protein in the R4 strain, we present its values as an exemplary model (Figure S2 in the Supplementary Materials)

Summary

Introduction

The pyridine ring system can be found in a number of natural products and in several pharmacologically relevant compounds. 2-amino-4-aryl-3,5-dicarbonitrile6-thiopyridines have gained considerable attention due to their wide-ranging biological activities (Figure 1) [1].

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