title: Substituent Effects on Cytotoxic Activity, Spectroscopic Property, and DNA Binding Property of Naphthalimide Derivatives.
abstract: A series of novel naphthalimide derivatives NI1-5 containing piperazine moieties (N-(2-hydroxyethyl)piperazine and 1-piperazinepropanol) and piperidine moieties (4-piperidinemethanol, 4-hydroxypiperidine and 4-piperidineethanol) have been synthesized and evaluated for their cytotoxic activity, spectroscopic property, and DNA binding behaviors. It was found that substituents at the 4-position remarkably influence the various activities of this series of compound. Compounds NI3-5 modified with piperidines exhibited potent cytotoxic activities against Hela, SGC-7901, and A549 cells with the IC50 values from 0.73 μm to 6.80 μm, which are better than NI1-2 functionalized with piperazines. Compounds NI1-2 showed higher binding capacity with Ct-DNA than compounds NI3-5 based on studies of UV-vis, fluorescence and CD spectra. Furthermore, compounds NI3-5, as DNA intercalators, showed fluorescence enhancement upon binding with Ct-DNA. More interestingly, fluorescence imaging studies of compound NI4 with A549 cells showed that the fluorescence predominantly appeared in the cytoplasm. These results provided a potential application of NI3-5 as anticancer therapeutic and cancer cell imaging agents.
authors.affiliation: Key Laboratory of Chemical Biology of Hebei Province, College of Chemistry and Environmental Science, Hebei University, Baoding, 071002, China.|Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of Ministry of Education, Baoding, 071002, China.
authors.forename: Ke-Rang
authors.initials: KR
authors.lastname: Wang
authors.affiliation: Key Laboratory of Chemical Biology of Hebei Province, College of Chemistry and Environmental Science, Hebei University, Baoding, 071002, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Qian
authors.affiliation: Key Laboratory of Chemical Biology of Hebei Province, College of Chemistry and Environmental Science, Hebei University, Baoding, 071002, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Sun
authors.affiliation: Key Laboratory of Chemical Biology of Hebei Province, College of Chemistry and Environmental Science, Hebei University, Baoding, 071002, China.
authors.forename: Cui-Lan
authors.initials: CL
authors.lastname: Ma
authors.affiliation: Department of Immunology, School of Basic Medical Science, Hebei University, Baoding, China.
authors.forename: Rui-Xue
authors.initials: RX
authors.lastname: Rong
authors.affiliation: Department of Immunology, School of Basic Medical Science, Hebei University, Baoding, China.
authors.forename: Zhi-Ran
authors.initials: ZR
authors.lastname: Cao
authors.affiliation: Department of Immunology, School of Basic Medical Science, Hebei University, Baoding, China.
authors.forename: Xiao-Man
authors.initials: XM
authors.lastname: Wang
authors.affiliation: Key Laboratory of Chemical Biology of Hebei Province, College of Chemistry and Environmental Science, Hebei University, Baoding, 071002, China.|Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of Ministry of Education, Baoding, 071002, China.
authors.forename: Xiao-Liu
authors.initials: XL
authors.lastname: Li
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004247:DNA / Q000737:chemistry*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D009281:Naphthalenes / Q000737:chemistry / Q000494:pharmacology*; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D000970:Antineoplastic Agents; D009281:Naphthalenes; D004247:DNA
keywords: DNA binding; cytotoxicity; fluorescence imaging; naphthalimide; piperidine