Indolequinone-rhodol conjugate as a fluorescent probe for hypoxic cells: enzymatic activation and fluorescence properties

被引：66

作者：

Komatsu, Hirokazu ^{[1
,2
]}

Harada, Hiroshi ^{[3
]}

Tanabe, Kazuhito ^{[1
]}

Hiraoka, Masahiro ^{[4
]}

Nishimoto, Sei-ichi ^{[1
]}

机构：

[1] Kyoto Univ, Dept Energy & Hydrocarbon Chem, Grad Sch Engn, Nishikyo Ku, Kyoto 6158510, Japan

[2] ASTEM, Kyoto City Collaborat Reg Entities Advancement Te, Kyoto 6158510, Japan

[3] Kyoto Univ, Grp Radiat & Tumor Biol, Career Path Promot Unit Young Life Scientists, Sakyo Ku, Kyoto 6068501, Japan

[4] Kyoto Univ, Dept Radiat Oncol & Image Appl Therapy, Grad Sch Med, Sakyo Ku, Kyoto 6068507, Japan

来源：

MEDCHEMCOMM | 2010年 / 1卷 / 01期

关键词：

HETEROCYCLIC SIDE-CHAINS; BIOLOGICAL EVALUATION; BIOREDUCTIVE BINDING; ANTITUMOR AGENTS; SOLID TUMOR; MARKERS; ELIMINATION; DERIVATIVES; PRODRUGS; SENSORS;

D O I：

10.1039/c0md00024h

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Hypoxia is an important feature of many diseases such as malignant solid tumors, inflammatory diseases and cardiac ischemia. We herein focused on the development of a novel hypoxia-sensitive fluorescent probe, IQ-R, consisting of an indolequinone unit and a rhodol fluorophore. IQ-R has good solubility in water and longer wavelength for absorption and emission, which are favorable for cellular bioimaging. While the fluorescence of rhodol in the IQ-R conjugate was quenched by the function of intramolecular indolequinone unit, it was restored under hypoxic conditions through the enzymatic one-electron reduction of IQ-R by NADPH:cytochrome P450 reductase to release the nonconjugated free rhodol. When administered to A549 cells, IQ-R was activated and reduced by endogenous reductase preferentially under hypoxic conditions, thereby visualizing hypoxic cancer cells by robust fluorescence.

引用

页码：50 / 53

页数：4

共 27 条

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