δ-Lactones—A New Class of Compounds That Are Toxic to E. coli K12 and R2–R4 Strains

Abstract

Lactones are among the well-known organic substances with a specific taste and smell. They are characterized by antibacterial, antiviral, anti-inflammatory, and anti-cancer properties. In recent years, among this group of compounds, new biologically active substances have been searched by modifying the main (leading) structure with new analogs with stronger or different responses that may have a toxic effect on the cells of pathogenic bacteria and constitute an alternative to commonly used antibiotics. A preliminary study of δ-lactone derivatives as new potential candidates for antibacterial drugs was conducted. Particular emphasis was placed on the selection of the structure of lactones with the highest biological activity, especially those with fluorine in their structure as a substituent in terms of action on bacterial lipopolysaccharide (LPS) in the model strains of Escherichia coli K12 (without LPS in its structure) and R2–R4 (LPS of different lengths in its structure). In the presented studies, on the basis of the conducted MIC and MBC tests, it was shown that the antibacterial (toxic) activity of lactones depends on their structure and the length of the bacterial LPS in the membrane of specific strains. Moreover, oxidative damage of bacterial DNA isolated from bacteria after modification with newly synthesized compounds after application of the repair enzyme Fpg glycosylase was analyzed. The analyzed damage values were compared with the modification with appropriate antibiotics: ciprofloxacin, bleomycin, and cloxacillin. The presented research clearly shows that lactone derivatives can be potential candidates as substitutes for drugs, e.g., the analyzed antibiotics. Their chemical and biological activity is related to coumarin derivatives and the corresponding δ-lactone groups in the structure of the substituent. The observed results are of particular importance in the case of increasing bacterial resistance to various drugs and antibiotics, especially in nosocomial infections and neoplasms, and in the era of a microbial pandemic.

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

“…After treatment with Fpg glycosase in strain R4, we observed clearly visible damage in the topological changes in plasmid DNA forms; “ccc”, linear form and “oc”, which have been completely damaged and are only visible as stray bands (see Figure 6 , Figures S2 and S3 in the Supplementary Materials ) according to the earlier literature (data [ 45 , 46 , 47 , 48 , 49 , 50 ]).…”

“…In our current studies into the toxicity of pyridine derivatives on model E. coli bacterial cells, we used MIC and MBC tests, similar to our earlier experiments [ 45 , 46 , 47 , 48 , 49 , 50 ]. They consisted of examining the rate of migration of the analyzed compounds through the bacterial membranes that may be damaged by them, which, in turn, may lead to apoptosis of the bacterial cell.…”

“…They consisted of examining the rate of migration of the analyzed compounds through the bacterial membranes that may be damaged by them, which, in turn, may lead to apoptosis of the bacterial cell. This is especially visible when the color of the analyzed sample changes after the addition of a special resazurin dye, which changes its color from dark blue to pink, orange or yellow [ 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 ]. As a result of irreversible damage to the bacterial membrane by a given compound, the dye penetrates with varying intensity, but only reaches dead cells ( Figures S1–S3 in Supplementary Materials ).…”

“…No such visible and significant changes in the structure were observed in the bacterial DNA obtained and modified from other strains, K12, R2 and R3. For further analysis with the Fpg protein (which is a bifunctional glycosylase and recognizes oxidized DNA bases such as 8oxoG, FapyA and FapyG) [ 45 , 46 , 47 , 48 , 49 , 50 ], we used plasmid DNA. 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 ).…”

“…All bacterial strains were received and statistically analysed, as described in [ 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 ].…”