Ferrocene appended naphthalimide derivatives: Synthesis, DNA binding, and in vitro cytotoxic activity

• Published in: Journal of organometallic chemistry Vol. 888; pp. 16 - 23
• Main Authors: Jia, Deng-Guo, Zheng, Jia-An, Fan, Yan-Ru, Yu, Jian-Qiang, Wu, Xiu-Li, Wang, Bo-Jin, Yang, Xin-Bin, Huang, Yu
• Format: Journal Article
• Language: English
• Published: LAUSANNE Elsevier B.V 15.06.2019; Elsevier
• Subjects: Chemistry; Chemistry, Inorganic & Nuclear; Chemistry, Organic; Cytotoxicity; DNA binding; Ferrocene; Naphthalimide derivatives; Physical Sciences; Science & Technology; Synthesis; Cytotoxicity; Naphthalimide derivatives; Synthesis; DNA binding; Ferrocene; DESIGN; SERIES; INTERCALATORS; COMPLEXES; BIS; DAMAGE; ANTICANCER; FLUORESCENCE
• ISSN: 0022-328X; 1872-8561
• DOI: 10.1016/j.jorganchem.2019.03.001

Three novel ferrocene appended naphthalimide derivatives (2a, 2b and 6) were synthesized and characterized by IR, 1H NMR and mass spectroscopies. In electrochemical experiments, all of the ferrocene appended naphthalimide derivatives exhibited reversible one-electron oxidation in CV curves. And the DNA binding ability of the compounds was studied by ethidium bromide displacement experiments and UV–visible spectrophotometry. The ferrocene appended naphthalimide derivative 6 also exhibited the highest DNA binding ability in all the tested compounds. According to the viscosity results, all of the synthesized compounds displayed the partial intercalation binding mode to DNA duplex. Bis-naphthalimide compound 5 was used as reference compound to evaluate the synergistic effect of the ferrocene group in ferrocene appended naphthalimide derivative 6. The cytotoxicity of the synthesized compounds against 4 different human cancer cell lines (EC109, BGC823, SGC 7901 and HepG2) was studied by MTT assay. The ferrocene appended bis-naphthalimide derivative 6 showed the best cytotoxicity against tested human cancer cells in all the synthesized naphthalimide derivatives and control drug amonafide. The uptake of naphthalimide derivative 6 was proved by laser confocal images. In addition, the DNA damage induced by naphthalimide derivative 6 was studied by comet assay. [Display omitted] •Bis-naphthalimide with suitable linker is helpful to improve the cytotoxicity.•Bis-naphthalimide with ferrocene exhibit synergistic effect in cytotoxicity.•The cytotoxicity is due to DNA damage in cancer cells.