Abstract

The escalating crisis of antibiotic resistance necessitates the development of novel antimicrobial agents with distinct mechanisms of action. This study investigates the synthesis and biological activity of a new class of **cationic lipoaminoacid derivatives of diethanolamine** as potential membrane-active antibacterial agents. The objective was to design molecules that leverage the synergistic properties of a cationic head group and a lipophilic tail to disrupt bacterial cell membranes. A series of derivatives were successfully synthesized and characterized using spectroscopic methods. Their antibacterial efficacy was evaluated against a panel of Gram-positive and Gram-negative bacteria, revealing potent activity, particularly against multi-drug resistant strains. Mechanistic studies, including liposome leakage assays and zeta potential measurements, confirmed that the primary mode of action involves rapid and concentration-dependent disruption of the bacterial cell membrane integrity, consistent with a detergent-like mechanism. These findings demonstrate that the novel cationic lipoaminoacid derivatives represent a promising scaffold for developing next-generation antimicrobial therapeutics that bypass traditional resistance pathways by targeting the fundamental structure of the bacterial membrane.