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Siderophore-antibiotic conjugate design: New drugs for bad bugs?

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journal contribution
posted on 22.05.2020, 11:08 by KH Negash, JKS Norris, JT Hodgkinson
Antibiotic resistance is a global health concern and a current threat to modern medicine and society. New strategies for antibiotic drug design and delivery offer a glimmer of hope in a currently limited pipeline of new antibiotics. One strategy involves conjugating iron-chelating microbial siderophores to an antibiotic or antimicrobial agent to enhance uptake and antibacterial potency. Cefiderocol (S-649266) is a promising cephalosporin-catechol conjugate currently in phase III clinical trials that utilizes iron-mediated active transport and demonstrates enhanced potency against multi-drug resistant (MDR) Gram-negative pathogens. Such molecules demonstrate that siderophore-antibiotic conjugates could be important future medicines to add to our antibiotic arsenal. This review is written in the context of the chemical design of siderophore-antibiotic conjugates focusing on the differing siderophore, linker, and antibiotic components that make up conjugates. We selected chemically distinct siderophore-antibiotic conjugates as exemplary conjugates, rather than multiple analogues, to highlight findings to date. The review should offer a general guide to the uninitiated in the molecular design of siderophore-antibiotic conjugates.

Funding

J.T. Hodgkinson′s preliminary research into siderophore–antibiotic conjugates was funded by The RoyalSociety grant number RG170080

History

Citation

Molecules 2019, 24(18), 3314; https://doi.org/10.3390/molecules24183314

Version

VoR (Version of Record)

Published in

Molecules

Volume

24

Issue

18

Pagination

3314 - 3314

Publisher

MDPI AG

issn

1420-3049

eissn

1420-3049

Acceptance date

10/09/2019

Copyright date

2019

Language

eng