Synthesis and antimicrobial activity of an SO2-releasing siderophore conjugate

TY - JOUR

T1 - Synthesis and antimicrobial activity of an SO2-releasing siderophore conjugate

AU - Black, Conor

AU - Chu, Adrian J

AU - Thomas, Gavin H

AU - Routledge, Anne

AU - Duhme-Klair, Anne-Kathrin

N1 - Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

PY - 2022/9

Y1 - 2022/9

N2 - A novel Trojan Horse conjugate consisting of an SO2-releasing 2,4-dinitrobenzenesulfonamide group attached to the monocatecholate siderophore aminochelin was synthesized to examine whether a bidentate catecholate siderophore unit could help potentiate the antimicrobial activity of SO2-releasing prodrugs. The conjugate obtained displays rapid SO2 release on reaction with glutathione, and proved more active against S. aureus than a comparable SO2-releasing prodrug lacking the siderophore unit, although activity required micromolar concentrations. The conjugate was inactive against wild-type E. coli, but activity was observed against an entA mutant strain that is unable to produce its major siderophores. Hence, the poor activity of the conjugate in wild-type E. coli may be due to the production of native siderophores that can compete with the conjugate for iron binding and uptake.

AB - A novel Trojan Horse conjugate consisting of an SO2-releasing 2,4-dinitrobenzenesulfonamide group attached to the monocatecholate siderophore aminochelin was synthesized to examine whether a bidentate catecholate siderophore unit could help potentiate the antimicrobial activity of SO2-releasing prodrugs. The conjugate obtained displays rapid SO2 release on reaction with glutathione, and proved more active against S. aureus than a comparable SO2-releasing prodrug lacking the siderophore unit, although activity required micromolar concentrations. The conjugate was inactive against wild-type E. coli, but activity was observed against an entA mutant strain that is unable to produce its major siderophores. Hence, the poor activity of the conjugate in wild-type E. coli may be due to the production of native siderophores that can compete with the conjugate for iron binding and uptake.

U2 - 10.1016/j.jinorgbio.2022.111875

DO - 10.1016/j.jinorgbio.2022.111875

M3 - Article

C2 - 35661473

SN - 0162-0134

VL - 234

JO - JOURNAL OF INORGANIC BIOCHEMISTRY

JF - JOURNAL OF INORGANIC BIOCHEMISTRY

M1 - 111875

ER -