Nitroreductase-activated nitric oxide (NO) prodrugs

被引：41

作者：

Sharma, Kavita ^{[1
]}

Sengupta, Kundan ^{[2
]}

Chakrapani, Harinath ^{[1
]}

机构：

[1] Indian Inst Sci Educ & Res Pune, Dept Chem, Pune, Maharashtra, India

[2] Indian Inst Sci Educ & Res Pune, Dept Biol, Pune, Maharashtra, India

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2013年 / 23卷 / 21期

基金：

英国惠康基金;

关键词：

Nitric oxide; Prodrug; Nitroreductase; Diazeniumdiolate; Directed prodrug therapy; ESCHERICHIA-COLI NITROREDUCTASE; DIRECTED ENZYME; IN-VITRO; !text type='JS']JS[!/text]-K; DIAZENIUMDIOLATE; CANCER; DONORS; THERAPY; HYPOXIA; CHEMISTRY;

D O I：

10.1016/j.bmcl.2013.08.066

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Due to the involvement of nitric oxide (NO) in numerous and diverse physiological processes, site-directed delivery of therapeutic NO in order to minimize unwanted side-effects is necessary. O-2-(4-Nitrobenzyl) diazeniumdiolates are designed as substrates for Escherichia coli nitroreductase (NTR), an enzyme that is frequently used to facilitate directed delivery of cytotoxic species to cancers. O-2-(4-Nitrobenzyl) diazeniumdiolates are found to be stable in aqueous buffer but are metabolized by NTR to produce NO. A cell viability assay revealed that cytotoxic effects of O-2-(4-nitrobenzyl)1-(2-methylpiperidin-1-yl)diazen-1-ium-1,2-diolate (4b) towards two cancer cell lines is significantly enhanced in the presence of NTR suggesting the potential for use of this compound in nitric oxide-based directed prodrug therapy. (C) 2013 Elsevier Ltd. All rights reserved.

引用

页码：5964 / 5967

页数：4

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