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.

Novel Hydroxamic Acids Containing Aryl-Substituted 1,2,4- or 1,3,4-Oxadiazole Backbones and an Investigation of Their Antibiotic Potentiation Activity

“…Severe sepsis caused by bacterial infections affects up to 18 million people worldwide each year, with mortality rates ranging from 28% to 50% [ 1 , 4 ]. Bacterial infections are a major health problem in the world, and the treatment of these infectious diseases is becoming increasingly difficult given the development of antibiotic resistance [ 5 , 6 , 7 , 8 , 9 , 10 ]. Back in 1945, Alexander Fleming, who discovered penicillin, warned that bacteria could become resistant to antibiotics in the future.…”

“…The development of resistance to antibiotics is a natural evolutionary process for microorganisms. The development of antibiotic resistance is aggravated by the uncontrolled use of antibiotics in medicine and agriculture [ 6 ]. Resistant strains can multiply and spread where infection prevention and control measures are not followed.…”