一种缺氧激活型抗菌前药。

A hypoxia-activated antibacterial prodrug.

机构信息

ARC Centre of Excellence for Nanoscale BioPhotonics (CNBP), Department of Chemistry, The University of Adelaide, North Terrace, Adelaide, SA 5005, Australia.

School of Biological Sciences, Department of Molecular and Cellular Biology, The University of Adelaide, North Terrace, Adelaide, SA 5005, Australia.

出版信息

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

DOI:10.1016/j.bmcl.2020.127140

PMID:32247730

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.

摘要

据报道，一种基于已知抗菌化合物的前药在还原条件下针对金黄色葡萄球菌和大肠杆菌。该前药通过将一个赖氨酸残基的 N 末端和侧链胺作为 4-硝基苄基氨基甲酸酯进行掩蔽来制备。用模型还原剂二氯化锡处理证明了释放抗菌剂的激活作用。化合物 1 的生物活性在抗菌药敏试验中得到证实，而前药 2 则没有活性。