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

Paweł Kowalczyk; Barbara Gawdzik; Damian Trzepizur; Mateusz Szymczak; Grzegorz Skiba; Stanisława Raj; Karol Kramkowski; Rafał Lizut; Ryszard Ostaszewski

doi:10.3390/ma14112956

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

Materials (Basel). 2021 May 30;14(11):2956. doi: 10.3390/ma14112956.

Authors

Paweł Kowalczyk¹, Barbara Gawdzik², Damian Trzepizur³, Mateusz Szymczak⁴, Grzegorz Skiba¹, Stanisława Raj¹, Karol Kramkowski⁵, Rafał Lizut⁶, Ryszard Ostaszewski³

Affiliations

¹ Department of Animal Nutrition, The Kielanowski Institute of Animal Physiology and Nutrition, Polish Academy of Sciences, 05-110 Jabłonna, Poland.
² Institute of Chemistry, Jan Kochanowski University, Swietokrzyska 15 G, 25-406 Kielce, Poland.
³ Institute of Organic Chemistry PAS, Kasprzaka 44/52, 01-224 Warsaw, Poland.
⁴ Department of Molecular Virology, Institute of Microbiology, Faculty of Biology, University of Warsaw, Miecznikowa 1, 02-096 Warsaw, Poland.
⁵ Department of Physical Chemistry, Medical University of Bialystok, Kilińskiego 1 str, 15-089 Bialystok, Poland.
⁶ Department of Mathematics, Informatics and Landscape Architecture, Institute of Informatics, The John Paul II Catholic University of Lublin, 20-708 Lublin, Poland.

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.

Keywords: E. coli strains; antibiotics; lipopolysaccharide; oxidative stress; δ-lactones.