Exploring the Antibacterial Potential of Bis-MPA Dendrimers Bearing Cu(II) and Zn(II) Complexes

The rise of multidrug-resistant bacteria demands antimicrobial agents that act rapidly and durably. In this work, we aim to develop biodegradable and biocompatible antimicrobial systems by combining the versatile bis-MPA dendritic skeleton with the antibacterial properties of Zn(II) and Cu(II) complexes. The resulting metallodendrimers were synthesized using scalable bis-MPA scaffolds and systematically evaluated for antibacterial activity, cytotoxicity, resistance development and bactericidal kinetics. The dendrimers exhibit broad-spectrum antibacterial efficacy at low micromolar concentrations, with minimum inhibitory concentration values as low as 0.4 μM, while maintaining over 70% viability in fibroblasts and keratinocytes and showing no hemolytic activity toward erythrocytes at bactericidal doses. Second-generation Cu(II) and Zn(II) bis-MPA dendrimers eradicated Bacillus subtilis within 24 h and suppressed Pseudomonas aeruginosa within 4 h, without detectable resistance emergence and with superior activity to ciprofloxacin in the latter. Overall, the combination of rapid antimicrobial action, favorable cytotoxicity profiles, strain-dependent resistance behavior, and scaffold versatility highlights bis-MPA metallodendrimers as promising candidates for next-generation antimicrobial therapies.