Cyclodextrin-siderophore conjugates as a Trojan horse strategy for bacterial targeting

The rise of antibiotic resistance necessitates the development of innovative strategies to enhance the effectiveness of existing treatments. One promising approach leverages bacterial iron acquisition systems through siderophore-based drug delivery to increase intracellular drug concentrations, a Trojan horse strategy. We synthesized new cyclodextrin conjugates with siderophores, such as deferoxamine and gallic acid, to exploit the cyclodextrin drug inclusion capability within the Trojan horse strategy. These novel derivatives were investigated as doxycycline carriers in the bacteria Escherichia coli and Staphylococcus aureus. Notably, the cyclodextrin deferoxamine derivative significantly enhanced the doxycycline efficacy by a 4-fold improvement of its minimal inhibitory concentration against Escherichia coli.