文献类型：期刊文献

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

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

年份：2008

卷号：16

期号：15

起止页码：7107

外文期刊名：BIOORGANIC & MEDICINAL CHEMISTRY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000258749500003)】；

基金：Dr. Ingo Ott appreciates a postdoctoral fellowship from East China University of Science and Technology.

语种：英文

外文关键词：antitumor drugs; naphthalimides; phototoxicity; photodynamic therapy; photoinduced electron transfer (PET)

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.