Abstract
The increasing emergence of multidrug-resistant microorganisms poses one of the most significant challenges in the clinical management of infectious diseases. This situation has made it necessary to research new, effective antimicrobial agents. The amino acid skeleton is vital for biological activities. Therefore, amino acid-based derivatives, which constitute a group of compounds with various biological activities, have found many applications in the medical field due to their high levels of biocompatibility and biodegradability. In this study, the antimicrobial and antibiofilm effects of some water-soluble amino acid alkyl esters (glycine benzyl ester, glycine t-butyl ester, glycine ethyl ester, l-phenylalanine benzyl ester, l-phenylalanine t-butyl ester, and l-phenylalanine ethyl ester) were investigated against the causative agents of hospital-acquired infections and strong biofilm formers, Escherichia coli OR651248 and Staphylococcus aureus ATCC 25923. Minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) were determined by the broth dilution method. The Kirby-Bauer disk diffusion method was used to assess zones of inhibition (ZOIs), and biofilm formation was established by using the crystal violet binding assay. Amino acid esters exhibited notable antimicrobial and antibiofilm activities, suggesting their potential as alternative or adjunct antimicrobial candidates, and l-phenylalanine benzyl ester emerged as the most antimicrobial ester among all esters and showed the lowest MIC (1.56 mg/mL) and MBC (3.12 mg/mL) values against both Escherichia coli OR651248 and Staphylococcus aureus ATCC 25923 strains. Additionally, it was determined that glycine esters had a more effective biofilm inhibitory effect compared with l-phenylalanine esters. Also, molecular docking studies, ADME properties, and drug-likeness were also reported to support experimental findings, and these molecules were evaluated for their potential as inhibitors against Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus using the antibacterial receptor (PDB:1HNJ). The theoretical docking simulations were performed with Autodock Vina software. These new findings, specific to this study, are thought to provide valuable data on the antimicrobial and antibiofilm effects of amino acid esters and contribute to the development of new synthesizable drug studies.