Conjugation of Aztreonam, a Synthetic Monocyclic β-Lactam Antibiotic, to a Siderophore Mimetic Significantly Expands Activity Against Gram-Negative Bacteria

Overview

Journal ACS Infect Dis

Specialties Infectious Diseases
Microbiology
Pharmacology

Date 2021 Oct 20

PMID 34668698

Citations 2

Authors

Rui Liu

Patricia A Miller

Marvin J Miller

Affiliations

Soon will be listed here.

Abstract

Monocyclic β-lactams with antibiotic activity were first synthesized more than 40 years ago. Extensive early structure-activity relationship (SAR) studies, especially in the 1980s, emphasized the need for heteroatom activation of monocyclic β-lactams and led to studies of oxamazins, monobactams, monosulfactams, and monocarbams with various side chains and peripheral substitution that revealed potent activity against select strains of Gram-negative bacteria. Aztreonam, still the only clinically used monobactam, has notable activity against many Gram-negative bacteria but limited activity against some of the most problematic multidrug resistant (MDR) strains of and . Herein, we report that extension of the side chain of aztreonam is tolerated and especially that coupling of the side chain free acid with a bis-catechol siderophore mimetic significantly improves activity against the MDR strains of Gram-negative bacteria that are of most significant concern.

Citing Articles

High-Throughput Discovery of Synthetic Siderophores for Trojan Horse Antibiotics.

Weber B, Ritchie N, Hilker S, Chan D, Peukert C, Deisinger J ACS Infect Dis. 2024; 10(11):3821-3841.

PMID: 39438291 PMC: 11556397. DOI: 10.1021/acsinfecdis.4c00359.

Siderophore conjugates to combat antibiotic-resistant bacteria.

Rayner B, Verderosa A, Ferro V, Blaskovich M RSC Med Chem. 2023; 14(5):800-822.

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