Sulfur-substituted naphthalimides as photoactivatable anticancer agents: DNA interaction, fluorescence imaging, and phototoxic effects in cultured tumor cells
| Autor: | Ingo Ott, Jianwen Liu, William S. Sheldrick, Melanie Harlos, Yufang Xu, Malte Kokoschka, Xuhong Qian |
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| Rok vydání: | 2008 |
| Předmět: |
Fluorescence-lifetime imaging microscopy
Biodistribution Time Factors medicine.medical_treatment Clinical Biochemistry Pharmaceutical Science Antineoplastic Agents Photodynamic therapy Biochemistry Fluorescence Inhibitory Concentration 50 Structure-Activity Relationship chemistry.chemical_compound Cell Line Tumor Drug Discovery medicine Humans Molecular Biology Benzofurans Flavonoids Dose-Response Relationship Drug Molecular Structure biology Chemistry Topoisomerase Organic Chemistry DNA Naphthalimides Photochemotherapy Drug Design biology.protein Molecular Medicine Phototoxicity Dermatitis Phototoxic |
| Zdroj: | Bioorganic & Medicinal Chemistry. 16:7107-7116 |
| ISSN: | 0968-0896 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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