Enzymatic activation of indolequinone-substituted 5-fluorodeoxyuridine prodrugs in hypoxic cells

被引：11

作者：

Jiho, Yota ^{[1
]}

Kurihara, Ryohsuke ^{[1
]}

Kawai, Kiyohiko ^{[2
]}

Yamada, Hisatsugu ^{[3
]}

Uto, Yoshihiro ^{[3
]}

Tanabe, Kazuhito ^{[1
]}

机构：

[1] Aoyama Gakuin Univ, Coll Sci & Engn, Dept Chem & Biol Sci, Chuo Ku, 5-10-1 Fuchinobe, Sagamihara, Kanagawa 2525258, Japan

[2] Osaka Univ, Inst Sci & Ind Res SANKEN, Mihogaoka 8-1, Ibaraki, Osaka 5670047, Japan

[3] Tokushima Univ, Grad Sch Technol Ind & Social Sci, 2-1 Minamijyosanjima Cho, Tokushima 7708506, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2019年 / 29卷 / 11期

关键词：

Enzymatic activation; Prodrug; Tumor hypoxia; Reductase; TUMOR HYPOXIA; DESIGN; REDUCTION;

D O I：

10.1016/j.bmcl.2019.04.003

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Among the various enzymes, reductases that catalyze one-electron reduction are involved in the selective activation of functional compounds or materials in hypoxia, which is one of the well-known pathophysiological characteristics of solid tumors. Enzymatic one-electron reduction has been recognized as a useful reaction that can be applied in the design of tumor hypoxia-targeting drugs. In this report, we characterized the enzymatic reaction of 5-fluorodeoxyuridine (FdUrd) prodrug bearing an indolequinone unit (IQ-FdUrd), which is a substrate of reductases. IQ-FdUrd was activated to release FdUrd under hypoxic conditions after treatment with cytochrome NADPH P450 reductase. We also confirmed that IQ-FdUrd showed selective cytotoxicity in hypoxic tumor cells.

引用

页码：1304 / 1307

页数：4

共 21 条

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