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

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.

Promiscuous Lipase-Catalyzed Markovnikov Addition of H-Phosphites to Vinyl Esters for the Synthesis of Cytotoxic α-Acyloxy Phosphonate Derivatives

“…As a continuation of our research on sustainable protocols, [ 50 , 51 , 52 , 53 ] we paid attention to find an environmentally friendly method for desired α-hydroxy phosphonates 1 – 4 [ 16 ] and α-acyloxy phosphonates 5 – 10 ( Figure 2 ).…”

“…Modified bacterial DNA was digested by using Fpg protein. We wanted to observe whether the resulting modifications in bacterial DNA would introduce oxidative damage to the DNA chain by changing the topological three forms [ 50 , 57 , 58 , 59 , 60 , 61 , 62 ]. Probably the size of the specific substituent at α-position may determine the toxicity of the analyzed E. coli strains, including in particular R4, as evidenced by the obtained MIC and MBC values.…”

Relationship between Structure and Antibacterial Activity of α-Aminophosphonate Derivatives Obtained via Lipase-Catalyzed Kabachnik−Fields Reaction

“…The Kabachnik–Fields reaction is the most efficient method for the formation of carbon−phosphorus bonds using an aldehyde, amine, and H -phosphite. A number of other synthetic approaches have also been reported for the preparation of α-aminophosphonates [ 7 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 ]. These methods are generally conducted in the presence of various organic and inorganic bases [ 56 , 57 , ...…”

“…As a continuation of our research on seeking new catalytic activities of hydrolases [ 74 , 75 , 76 , 77 , 78 , 79 , 80 , 94 , 95 ], we focused our efforts on elaborating a sustainable metal-free method towards desired α-aminophosphonates 1 – 16 ( Figure 2 ).…”

Functionalised Anodised Aluminium Oxide as a Biocidal Agent

“…Until now, such compounds have not been tested for biological activity against pathogenic E. coli strains, so there is a need to clarify their role [ 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 ].…”