Siderophore-Antibiotic Conjugation Combating Antimicrobial Resistance

Abstract

Pathogenic bacteria scavenge ferric iron from the host for survival and proliferation using small-molecular chelators, siderophores1. Siderophore-antibiotic conjugates, also called sideromycins, which were designed based on a “Trojan Horse” strategy wherein features enabled active uptake to bypass the Gram-negative cell wall, have been expected to be an efficient weapon for multidrug resistant strains caused infections in the clinic2. Herein, the siderophore-antibiotic conjugates were introduced to enhance the antimicrobial activity against Gram-negative bacteria. Through an optimized 11 steps synthesis route based on Miller’s work3, succinylated protected siderophore was synthesized and conjugated with ciprofloxacin (S1-Cip). Furthermore, a symmetric iron chelator conjugated with ciprofloxacin (S2-Cip) was designed and synthesized to investigate the antibacterial activity.