Development of Membrane-Targeting Cannabigerol Derivatives as Potent Broad-Spectrum Antibacterial Agents

Abstract Purpose: This research aimed to develop novel membrane-targeting antibacterial agents via rational design and synthesis of hybrid compounds derived from cannabigerol (CBG) and antimicrobial peptide (AMP) motifs. This approach targeted key limitations of CBG, specifically its poor aqueous solubility, restricted activity against Gram-negative pathogens, and low bioavailability. By incorporating AMP domains, we intended to exploit their membrane-disruptive capability, thereby achieving enhanced broad-spectrum activity, diminished propensity for resistance, and improved pharmacological properties. Methods: A library of membrane-active cannabigerol derivatives was