Synthesis of a group of porphyrin derivative compounds with potential photodynamic properties and investigation of their antibacterial effects against multidrug-resistant Escherichia coli
Project no. 29545 · Status: Kapanmış (Yayın bekleniyor) · 2023
Summary
<p>Antimicrobial resistance (AMR) is the ability of microorganisms to withstand the effects of antimicrobial agents and has emerged as a serious global public health problem, causing approximately 700,000 deaths annually. In particular, pathogens such as <em>Staphylococcus aureus</em>, <em>Escherichia coli</em>, <em>Pseudomonas aeruginosa</em>, and <em>Acinetobacter baumannii</em> that exhibit multidrug resistance (MDR) are frequently isolated from chronic wound infections, including surgical site infections, traumatic wounds, burns, and diabetic foot ulcers, significantly complicating the treatment of infected wounds. Carbapenem-resistant <em>A. baumannii</em> and <em>P. aeruginosa</em>, as well as carbapenem-resistant and extended-spectrum β-lactamase (ESBL)-producing <em>E. coli</em> and other members of the Enterobacteriaceae family, are considered priority pathogens due to their MDR characteristics and pose a major threat to human health, making them key targets for the development of new antibacterial agents.</p><p>Currently, antibacterial photodynamic therapy (aPDT), which has a low potential for inducing resistance, represents a promising strategy for the treatment of non-healing localized infected wounds. Studies have reported that cationic porphyrin derivatives are efficient photosensitizers (PSs) for use in aPDT.</p><p>In our previous studies, cationic porphyrin derivatives synthesized via quaternization with different halides were found to exhibit strong photodynamic inactivation against MDR) bacterial strains, and cationic derivatives obtained using benzyl chloride showed higher antimicrobial activity. In line with these findings, in this study, a total of 12 tetra-cationic porphyrin derivatives containing 2-, 4-, and 2,6-disubstituted benzyl groups with potential photodynamic properties were synthesized, and their structures were confirmed by FT-IR, <sup>1</sup>H NMR, and elemental analysis. The antimicrobial potential of the synthesized compounds was evaluated by determining their MIC values against Gram-positive bacteria (<em>Staphylococcus aureus</em> and <em>Enterococcus faecalis</em>) and Gram-negative bacteria (<em>Escherichia coli</em> and <em>Pseudomonas aeruginosa</em>), and their antibacterial photodynamic activities were investigated against a multidrug-resistant <em>E. coli</em> strain, one of the major causative agents of wound infections. Their photodynamic inactivation potentials against <em>E. coli</em>, reactive oxygen species (ROS) generation, and the cytotoxicity they induced in L929 fibroblast cells were evaluated together.</p><p><strong>Keywords:</strong> Multidrug resistance, antimicrobial photodynamic therapy, aPDT, cationic porphyrin derivatives</p>