Cationic Lipoaminoacid Derivatives of Diethanolamine As Potentially Membrane-Active Antibacterial Agents

• Published in: Biochemistry (Moscow). Supplement series A, Membrane and cell biology Vol. 17; no. 2; pp. 148 - 155
• Main Authors: Guseva, M. K., Denieva, Z. G., Budanova, U. A., Sebyakin, Yu. L.
• Format: Journal Article
• Language: English
• Published: Moscow Pleiades Publishing 01.06.2023; Springer Nature B.V
• Subjects: Amino acids; Antibacterial activity; Antibacterial agents; Antimicrobial activity; Antimicrobial agents; Biomedical and Life Sciences; Cations; Cell Biology; Diethanolamine; Domains; E coli; Gram-negative bacteria; Hydrophobicity; Life Sciences; Membranes; Minimum inhibitory concentration; Molecular chains; γ-Aminobutyric acid; diethanolamine; peptidomimetics; cationic amphiphiles; amino acid derivatives; bacterial resistance; antimicrobial peptides
• ISSN: 1990-7478; 1990-7494
• DOI: 10.1134/S1990747823020034

This work is aimed to develop several cationic amphiphiles based on amino acid derivatives of diethanolamine as potentially membrane-active antibacterial agents. The developed compounds contain two amino acid residues in the polar block and aliphatic chains of various length in the hydrophobic domain. Amphiphiles were obtained in preparative amounts sufficient to confirm their structures and perform a study of antibacterial activity. The synthesized samples based on β-Ala (4c) and GABA (4d) with aliphatic C12 chain in the hydrophobic domain showed a promising level of antimicrobial activity against gram-positive ( B. subtilis ) and gram-negative ( E. coli ) bacteria (minimal inhibitory concentration, MIC, 1 μg/mL). Amphiphiles containing aromatic amino acids L -Phe (6a) and L -Trp (6b) in the polar head group and C8 hydrocarbon chain exhibited an antibacterial activity against B. subtilis with MIC of 1 μg/mL. The obtained data on antimicrobial activity make the selected compounds attractive for further detailed study of their mechanism of action.