Toward Combating Pseudomonas aeruginosa Infection, the Creation of Azithromycin Derivatives Based on a Trojan Horse Strategy

Due to Pseudomonas aeruginosa (P. aeruginosa)'s inherent resistance to many antibiotics and the increasing incidence of multidrug-resistant (MDR) organisms, P. aeruginosa infection has become a growing global threat to humanity. Azithromycin (AZM) does not have prominent antibacterial activity against P. aeruginosa at a clinically reasonable level because of the bacteria's outer membrane and efflux pump system; however, it does demonstrate other properties, including reduction of inflammation and suppression of P. aeruginosa virulence. With the promising potential of AZM as an anti-P. aeruginosa active compound, we proposed the application of a Trojan horse strategy to the synthesis of AZM derivatives. In this study, we designed and synthesized catechol-conjugated AZM derivatives and evaluated their anti-P. aeruginosa activity. One of the derivatives showed superior antibacterial activity to AZM, even against MDR P. aeruginosa clinical isolates.