A hypoxia-activated antibacterial prodrug

Yuan Qi Yeoh; John R Horsley; Steven W Polyak; Andrew D Abell

doi:10.1016/j.bmcl.2020.127140

A hypoxia-activated antibacterial prodrug

Bioorg Med Chem Lett. 2020 Jun 1;30(11):127140. doi: 10.1016/j.bmcl.2020.127140. Epub 2020 Mar 27.

Authors

Yuan Qi Yeoh¹, John R Horsley¹, Steven W Polyak², Andrew D Abell³

Affiliations

¹ ARC Centre of Excellence for Nanoscale BioPhotonics (CNBP), Department of Chemistry, The University of Adelaide, North Terrace, Adelaide, SA 5005, Australia.
² School of Biological Sciences, Department of Molecular and Cellular Biology, The University of Adelaide, North Terrace, Adelaide, SA 5005, Australia. Electronic address: Steven.Polyak@unisa.edu.au.
³ ARC Centre of Excellence for Nanoscale BioPhotonics (CNBP), Department of Chemistry, The University of Adelaide, North Terrace, Adelaide, SA 5005, Australia. Electronic address: andrew.abell@adelaide.edu.au.

PMID: 32247730
DOI: 10.1016/j.bmcl.2020.127140

Abstract

A prodrug based on a known antibacterial compound is reported to target Staphylococcus aureus and Escherichia coli under reductive conditions. The prodrug was prepared by masking the N-terminus and side chain amines of a component lysine residue as 4-nitrobenzyl carbamates. Activation to liberate the antibacterial was demonstrated on treatment with a model reductant, tin(II) chloride. The bioactivity of 1 was confirmed in antibacterial susceptibility assays whereas prodrug 2 was inactive.

Keywords: Antibacterial; E. coli; Hypoxia-activated; Prodrug; S. aureus.

Publication types

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

MeSH terms

Anti-Bacterial Agents / chemical synthesis
Anti-Bacterial Agents / chemistry*
Anti-Bacterial Agents / pharmacology
Escherichia coli / drug effects
Microbial Sensitivity Tests
Prodrugs / chemical synthesis
Prodrugs / chemistry*
Prodrugs / pharmacology
Staphylococcus aureus / drug effects
Tin Compounds / pharmacology

Substances

Anti-Bacterial Agents
Prodrugs
Tin Compounds
stannous chloride