α-Amidoamids as New Replacements of Antibiotics—Research on the Chosen K12, R2–R4 E. coli Strains

Paweł Kowalczyk,Arleta Madej,Mateusz Szymczak,Ryszard Ostaszewski

doi:10.3390/ma13225169

Abstract

A preliminary study of α-amidoamids as new potential antimicrobial drugs was performed. Special emphasis was placed on selection of structure of α-amidoamids 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 R1–R4 (with different length LPS in its structure) were used. The presented work showed that the antibacterial activity of α-amidoamids depends on their structure and affects the LPS of bacteria. Moreover, the influence of various newly synthesized α-amidoamids on bacteria possessing smooth and rought LPS and oxidative damage of plasmid DNA caused by all newly obtained compounds was indicated. The presented studies clearly explain that α-amidoamids can be used as substitutes for antibiotics. The chemical and biological activity of the analysed α-amidoamids was associated with short alkyl chain and different isocyanides molecules in their structure such as: tetr-butyl isocyanide or 2,5-dimethoxybenzyl isocyanide. The observed results are especially important in the case of the increasing resistance of bacteria to various drugs and antibiotics.

Highlights

Peptides are essential for almost every physiological process in the cell
They contain appropriately chemically modified analogues synthesized on the basis of neuropeptides and peptide hormones, showing species-specific and organ-selective, directed physiological action, which significantly increases their stability under metabolic conditions, but retains biological activity [1,2,3,4]
The aim of our research was to check whether the interaction of Ugi reaction products depends on LPS length in Escherichia coli K-12 and R2–R4 strains that have different LPS in their outermost layer in the antigen “O” region

Summary

Introduction

Small peptides induced by endogenous factors such as hormones or exogenous e.g., active substances such as toxins have various biological activities [1,2,3,4] Such molecules, called peptidomimetics, appear to be an excellent starting material for the development of new candidate drugs that can mimic the structure or activity of natural peptides. They contain appropriately chemically modified analogues synthesized on the basis of neuropeptides and peptide hormones, showing species-specific and organ-selective, directed physiological action, which significantly increases their stability under metabolic conditions, but retains biological activity [1,2,3,4]. Methods for the synthesis of natural peptides are well known but the Materials 2020, 13, 5169; doi:10.3390/ma13225169 www.mdpi.com/journal/materials

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