title: Sulfur-substituted naphthalimides as photoactivatable anticancer agents: DNA interaction, fluorescence imaging, and phototoxic effects in cultured tumor cells.
abstract: 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.
authors.affiliation: State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Meilong Road 130, Shanghai 200237, China. ottingo@zedat.fu-berlin.de
authors.forename: Ingo
authors.initials: I
authors.lastname: Ott
authors.forename: Yufang
authors.initials: Y
authors.lastname: Xu
authors.forename: Jianwen
authors.initials: J
authors.lastname: Liu
authors.forename: Malte
authors.initials: M
authors.lastname: Kokoschka
authors.forename: Melanie
authors.initials: M
authors.lastname: Harlos
authors.forename: William S
authors.initials: WS
authors.lastname: Sheldrick
authors.forename: Xuhong
authors.initials: X
authors.lastname: Qian
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D001572:Benzofurans / Q000737:chemistry*; D045744:Cell Line, Tumor; D004247:DNA; D017484:Dermatitis, Phototoxic; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D005419:Flavonoids / Q000737:chemistry; D005453:Fluorescence; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D053644:Naphthalimides / Q000737:chemistry* / Q000494:pharmacology*; D010778:Photochemotherapy; D013329:Structure-Activity Relationship; D013997:Time Factors
chemical_list: D000970:Antineoplastic Agents; D001572:Benzofurans; D005419:Flavonoids; D053644:Naphthalimides; D004247:DNA; C054989:sulfuretin