Emerging Target-Directed Approaches for the Treatment and Diagnosis of Microbial Infections

J Med Chem. 2023 Jan 12;66(1):32-70. doi: 10.1021/acs.jmedchem.2c01212. Epub 2022 Dec 31.

Abstract

With the rising levels of drug resistance, developing efficient antimicrobial therapies has become a priority. A promising strategy is the conjugation of antibiotics with relevant moieties that can potentiate their activity by target-directing. The conjugation of siderophores with antibiotics allows them to act as Trojan horses by hijacking the microorganisms' highly developed iron transport systems and using them to carry the antibiotic into the cell. Through the analysis of relevant examples of the past decade, this Perspective aims to reveal the potential of siderophore-antibiotic Trojan horses for the treatment of infections and the role of siderophores in diagnostic techniques. Other conjugated molecules will be the subject of discussion, namely those involving vitamin B12, carbohydrates, and amino acids, as well as conjugated compounds targeting protein degradation and β-lactamase activated prodrugs.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents* / chemistry
  • Anti-Bacterial Agents* / pharmacology
  • Anti-Bacterial Agents* / therapeutic use
  • Siderophores* / chemistry

Substances

  • Siderophores
  • Anti-Bacterial Agents