Substituent Effects on Cytotoxic Activity, Spectroscopic Property, and DNA Binding Property of Naphthalimide Derivatives.

A series of novel naphthalimide derivatives NI 1-5 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 NI 3-5 modified with piperidines exhibited potent cytotoxic activities against Hela, SGC-7901, and A549 cells with the IC₅₀ values from 0.73 μ m to 6.80 μ m, which are better than NI 1-2 functionalized with piperazines. Compounds NI 1-2 showed higher binding capacity with Ct- DNA than compounds NI 3-5 based on studies of UV-vis, fluorescence and CD spectra. Furthermore, compounds NI 3-5, as DNA intercalators, showed fluorescence enhancement upon binding with Ct- DNA. More interestingly, fluorescence imaging studies of compound NI 4 with A549 cells showed that the fluorescence predominantly appeared in the cytoplasm. These results provided a potential application of NI 3-5 as anticancer therapeutic and cancer cell imaging agents. [ABSTRACT FROM AUTHOR]