Siderophore‑antibiotic conjugates: structural diversity and antibacterial activity

Abstract

Due to uncontrolled growth of antimicrobial resistance, in the near future humanity may return to the «pre-antibiotic era» with no reliable antimicrobial therapy even for previously easily treatable infectious diseases. One of possible solutions is improved delivery of antibiotics to antibiotic-resistant bacterial strains by conjugating them with siderophores (small molecules secreted by microorganisms to absorb essential Fe(III)). The siderophore-modified antibiotic (sideromycin), like a Trojan horse, permeates the bacterial cell as a complex with Fe(III), allowing the antibiotic to reach its biological target. In this review, we describe the structural diversity of siderophore-antibiotic conjugates with the focus on the structure of sideromycin as well as on the relationship between the structure of sideromycin and its antibacterial activity. We analyze main representatives of various classes of siderophores; the structural diversity of sideromycins and their antibacterial activity discussed in detail.