Rui-Xue Rong

Development of novel bis-naphthalimide derivatives and their anticancer properties

A series of novel N,N-bis(3-aminopropyl)methylamine-bridged bis-naphthalimide derivatives NI1–6 were designed and synthesized. Their cytotoxic activities against Hela, MCF-7, SGC-7901 and A549 cells were investigated. Compounds NI1–6 exhibited selectively cytotoxic activities in the tested cell lines and lower cytotoxic activities against MCF-7 cells were found except for compound NI1. NI1, the N-(2-hydroxyethyl)piperazine-modified naphthalimide, showed potent cytotoxic activity in the tested cell lines with IC50 values of 2.31, 2.94, 0.88 and 1.21 μM, respectively, better than the control drug (amonafide). Furthermore, its DNA binding properties, fluorescence imaging and collective apoptosis were investigated. Interestingly, NI1 as a DNA intercalator showed fluorescence enhancement upon binding with Ct-DNA and exhibited different impacts on the cell cycle compared with amonafide. Moreover, compound NI1 showed no significant hematoxicity and cardiotoxicity.

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

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.

Synthesis of novel sugar or azasugar modified anthra[1,2-d] imidazole-6,11-dione derivatives and biological evaluation

A series of novel, sugar or azasugar modified anthra[1,2-d] imidazole-6,11-dione derivatives, with different side chain were synthesized, using the synthetic route of imidazole cyclization reaction of 1,2-diaminoanthraquinone with various sugar (azasugar)-derived aldehydes, and imidazole cyclization reaction of 1,2-diaminoanthraquinone with chloroacetic acid and then followed by the nucleophilic substitution of N-alkylamino azasugar. Their biological activities against HIV-RT and cytotoxic activities against A549, Hela and MCF-7 cells were preliminary evaluated, most compounds showed similar HIV-RT inhibition to the control drug (AZT).

Lysosomes-targeting imaging and anticancer properties of novel bis-naphthalimide derivatives

A series of novel N,N-bis(3-aminopropyl)methylamine bridged bis-naphthalimide derivatives NI1-NI8 containing saturated nitrogenous heterocycles were designed and synthesized, their cytotoxic activities against Hela, MCF-7, A549 and MGC-803 cells were investigated, Compounds NI1-NI4 modified with piperidine and piperazine exhibited good and selective cytotoxic activity, for instance, compounds NI1 and NI4 showed potent cytotoxic activity against Hela cells and MGC-803 cells with the IC50 values of 2.89, 060, 2.73 and 1.60 μM, respectively, better than the control drug (Amonafide). However, compounds NI5-NI8 conjugated with pyrrole derivatives showed weak cytotoxic activities against the all tested cell lines. Furthermore, their DNA binding properties, fluorescence imaging and cell cycle were investigated. Interestingly, compounds NI1 and NI4 showed fluorescence enhancement because of the strong binding with Ct-DNA, and exhibited fluorescence imaging with Hela cells on the lysosomes.