Design, Synthesis, and Activity Evaluation of Novel Bifenamide Dual-Target Antibacterial Inhibitors and Carrier Based on Infectious Microenvironment

As the external environment worsens and immune function declines, Gram-negative bacterial infections are causing more and more serious pathological damage. In the study, three series of novel bifenamide dual-target (PD-L1/LpxC) compounds were designed using the skeleton growth method. Their chemical structures were synthesized, characterized, and evaluated for antibacterial activity. Among them, the compound <b>12b</b>, which exhibited excellent dual-target (PD-L1/LpxC) inhibition ability, could efficiently block the biosynthesis of bacterial lipopolysaccharide (LPS), leading to pathogenic cell lysis and death. Moreover, the nanocomposite (NC-<b>12b</b>) was also prepared based on the infection microenvironment to improve the bioavailability and targeting of compound <b>12b</b>. In vivo evaluation confirmed the dual functions of these components, including bacterial inhibition and immune activation, thereby synergistically accelerating the body's recovery process.