Sulfur-substituted naphthalimides as photoactivatable anticancer agents: DNA interaction, fluorescence imaging, and phototoxic effects in cultured tumor cells.
Sulfur-substituted naphthalimides as photoactivatable anticancer agents: DNA interaction, fluorescence imaging, and phototoxic effects in cultured tumor cells.
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DOI：
10.1016/j.bmc.2008.06.052
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发表时间：
2008-08
影响因子：
3.5
通讯作者：
I. Ott;Yufang Xu;Jianwen Liu;M. Kokoschka;M. Harlos;W. Sheldrick;X. Qian
中科院分区：
文献类型：
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作者：
I. Ott;Yufang Xu;Jianwen Liu;M. Kokoschka;M. Harlos;W. Sheldrick;X. Qian
合成了一系列硫取代萘酰亚胺类化合物，并研究了其抗肿瘤活性。最初的DNA相互作用研究（通过荧光猝灭法，UV/维斯和CD光谱，热变性，拓扑异构酶Western印迹分析，和DNA光裂解实验）表明DNA和拓扑异构酶的代理的主要目标。荧光光谱和显微镜实验表明3和5的发射强度对细胞环境的显著敏感性，并证实了1-3和5的细胞摄取和生物分布到细胞隔室中。在不同的实验设置（关于药物暴露期和额外的短时间UV照射）下的抗增殖作用的比较评价揭示了对环境敏感的化合物3和5的显着的光毒性作用，并强烈建议进一步开发硫取代的萘酰亚胺用于光动力学肿瘤治疗的潜在用途。
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.