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Siderophore–Antibiotic Conjugate Design: New Drugs for Bad Bugs?

Leicester Institute of Structural and Chemical Biology, School of Chemistry, University of Leicester, George Porter Building, University Road, Leicester LE1 7RH, UK
Author to whom correspondence should be addressed.
Academic Editor: Rainer Riedl
Received: 28 August 2019 / Revised: 9 September 2019 / Accepted: 10 September 2019 / Published: 11 September 2019
(This article belongs to the Special Issue Drug Design)
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. View Full-Text
Keywords: siderophore; antibiotic; siderophore–antibiotic; trojan horse; antibiotic resistance siderophore; antibiotic; siderophore–antibiotic; trojan horse; antibiotic resistance
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MDPI and ACS Style

Negash, K.H.; Norris, J.K.S.; Hodgkinson, J.T. Siderophore–Antibiotic Conjugate Design: New Drugs for Bad Bugs? Molecules 2019, 24, 3314.

AMA Style

Negash KH, Norris JKS, Hodgkinson JT. Siderophore–Antibiotic Conjugate Design: New Drugs for Bad Bugs? Molecules. 2019; 24(18):3314.

Chicago/Turabian Style

Negash, Kokob H.; Norris, James K.S.; Hodgkinson, James T. 2019. "Siderophore–Antibiotic Conjugate Design: New Drugs for Bad Bugs?" Molecules 24, no. 18: 3314.

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