Bis-quaternary ammonium BODIPY derivatives: Photophysical, antimicrobial, and antitumor photodynamic applications

Although Boron-dipyrromethene (BODIPY) derivatives have been explored for photodynamic antibacterial or antitumor applications, respectively, dual-activity cationic BODIPY photosensitizers have received much less attention. In addition, traditional quaternary ammonium compounds (QACs) are primarily studied as antibacterial agents, with systematic reports on their direct antitumor activity remaining scarce. We developed bis-quaternary ammonium cationic BODIPY derivatives as photosensitizers to investigate dual photodynamic antibacterial/antitumor action. All synthesized new compounds demonstrated notable UV-vis absorption in the range of 646-659 nm, intense fluorescence emission (665, 670, and 675 nm), and capabilities for reactive oxygen species (ROS) generation. Among these, brominated BODIPYs II₃ and II₅ exhibited high ROS generation efficiency and significant photodynamic antitumor activity against Eca-109 cells in vitro (IC₅₀ = 0.22 μM and 0.36 μM) and in vivo, comparable to the control drug m-THPC. Compounds I₅ and II₅ demonstrated substantial photodynamic antibacterial activities against pathogenic Staphylococcus aureus (S. aureus), with minimum inhibitory concentrations (MIC) of 0.5 μg/mL for both compounds. Furthermore, they achieved effective biofilm inhibition efficiencies of 86.74% and 85.23%, respectively, through the disruption of membrane integrity. These findings hold significant promise for pioneering new multifunctional photosensitizers that enable combined or sequential antimicrobial and antitumor photodynamic therapies.