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 12b, 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-12b) was also prepared based on the infection microenvironment to improve the bioavailability and targeting of compound 12b. In vivo evaluation confirmed the dual functions of these components, including bacterial inhibition and immune activation, thereby synergistically accelerating the body's recovery process.