Sulfur-substituted naphthalimides as photoactivatable anticancer agents: DNA interaction, fluorescence imaging, and phototoxic effects in cultured tumor cells

被引：77

作者：

Ott, Ingo ^{[1
,2
,3
]}

Xu, Yufang ^{[1
,2
]}

Liu, Jianwen ^{[1
,2
]}

Kokoschka, Malte ^{[4
]}

Harlos, Melanie ^{[4
]}

Sheldrick, William S. ^{[4
]}

Qian, Xuhong ^{[1
,2
]}

机构：

[1] E China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China

[2] E China Univ Sci & Technol, Shanghai Key Lab Chem Biol, Shanghai 200237, Peoples R China

[3] Free Univ Berlin, Inst Pharm, D-14195 Berlin, Germany

[4] Ruhr Univ Bochum, Lehrstuhl Analyt Chem, D-44780 Bochum, Germany

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2008年 / 16卷 / 15期

关键词：

antitumor drugs; naphthalimides; phototoxicity; photodynamic therapy; photoinduced electron transfer (PET);

D O I：

10.1016/j.bmc.2008.06.052

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：

A series of sulfur-substituted naphthalimides (1-5) was prepared and investigated as antitumor drugs. Initial DNA interaction studies (by the fluorescence quenching method, UV/vis and CD spectroscopy, thermal denaturation, topoisomerase Western blot analysis, and DNA photocleavage experiments) expectedly suggested the DNA and topoisomerase as main targets of the agents. Fluorescence spectroscopic and microscopic experiments indicated a significant sensitivity of the emission intensities of 3 and 5 to the cellular environment and confirmed the cellular uptake and biodistribution into cell compartments for 1-3 and 5. A comparative evaluation of the antiproliferative effects under different experimental setups (concerning drug exposure period and an additional short-time UV irradiation) revealed significant phototoxic effects for the environmentally sensitive compounds 3 and 5 and strongly suggested the further development of sulfur-substituted naphthalimides for potential use in photodynamic tumor therapy. (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：7107 / 7116

页数：10

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