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

M. K. Guseva; Гусева М. К.; Z. G. Denieva; Дениева З. Г.; U. A. Budanova; Буданова У. А.; Yu. L. Sebyakin; Себякин Ю. Л.

doi:10.31857/S0233475523020032

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

Authors: Guseva M.K.¹, Denieva Z.G.², Budanova U.A.¹, Sebyakin Y.L.¹
Affiliations:
1. MIREA, Russian Technology University, Lomonosov Institute of Fine Chemical Technology
2. Frumkin Institute of Physical Chemistry and Electrochemistry, Russian Academy of Sciences
Issue: Vol 40, No 2 (2023)
Pages: 133-141
Section: Articles
URL: https://rjmseer.com/0233-4755/article/view/667375
DOI: https://doi.org/10.31857/S0233475523020032
EDN: https://elibrary.ru/LANSBL
ID: 667375

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Abstract

This work is aimed to develop a number of 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 various length of aliphatic chains 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 an aliphatic C12 chain in the hydrophobic domain showed a promising level of antimicrobial activity (minimal inhibitory concentration, MIC, 1 μg/mL) against gram-positive (B. subtilis) and gram-negative (E. coli) bacteria. Amphiphiles containing aromatic amino acids L-Phe (6a) and L-Trp (6b) in the polar head group and C8 hydrocarbon chain are active against B. subtilis with a 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.

Keywords

antimicrobial peptides, peptidomimetics, cationic amphiphiles, diethanolamine, amino acid derivatives, bacterial resistance

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