Synthesis, DNA Binding, and Anticancer Properties of Bis-Naphthalimide Derivatives with Lysine-Modified Polyamine Linkers.

A series of bis-naphthalimide derivatives with different diamine linkers were designed and synthesized. All of the synthesized bis-naphthalimide derivatives were characterized by NMR and HRMS spectra. The binding ability between the compounds and CT DNA was evaluated by using UV-Vis titration experiments. The bis-naphthalimide compound with an ethylenediamine linker showed the largest binding constant with CT DNA. Hence, it was used as the model compound to study the DNA binding selectivity by UV-Vis titration aiming at different DNA duplexes. As a result, this compound showed binding preference to AT-rich duplexes. The DNA binding modes of the compounds were also measured by viscosity titration. The cytotoxicity of the compounds was evaluated by MTT assay. Compounds with 1,6-diaminohexane or 1,4-phenylenedimethanamine linkers showed higher cytotoxicity compared with other bis-naphthalimide derivatives.

[Diethylstilbestrol affects LGR8 expression in mouse gubernaculum testis].

OBJECTIVE: To investigate the impact of prenatal exposure to diethylstilbestrol (DES) on the specific receptor LGR8 of insulin-like factor 3 (INSL3) in the mouse gubernaculum testis, and that of exoestrogens on descensus testis in mice. METHODS: A total of 120 pregnant KM mice aged 8 to 10 weeks were assigned to a normal, a blank control and 4 DES groups of equal number, the blank controls injected subcutaneously with dimethyl sulfoxide plus normal saline, and the DES groups with DES at 0.1, 1, 10 and 100 microg/kg body weight, respectively, from embryonic day 9 (ED9) through ED17. Immunohistochemistry and RT-PCR were used to detect the expressions of LGR8 protein and mRNA in the gubernaculum testis of the ED18 fetuses and PND20 (postnatal day 20) offspring of the mice. RESULTS: Histological analysis showed that the gubernaculum testis of the ED18 fetuses were well developed in both the normal and control groups, with an inner mesenchymal core and muscular outer layer. In contrast, the gubernaculum testis were poorly developed in the experimental groups, morphologically abnormal and without visible dividing line between the mesenchymal tissue and the muscular outer layer. No obvious differences were found in the gubernaculum testis development of the neonates between the normal and experimental groups. Positive immunostaining was seen in the mesenchymal core and muscular outer layer, but mainly in the latter. The expression of LGR8 was weaker in the experimental groups than in the normal group (P < 0.05), but that of LGR8 mRNA was increased in the high-dose (10 and 100 microg/kg) DES groups (P < 0.05). No obvious mutations were observed in the PCR products in any of the experimental groups. CONCLUSION: Prenatal exposure to diethylstilbestrol affected the expression of LGR8 mRNA in the mouse gubernaculum testis, which suggests that diethylstilbestrol may induce cryptorchidism by interfering with the INSL3-LGR8 signaling system and consequently the development of the gubernaculum testis.

Synthesis, electrochemistry, DNA binding and in vitro cytotoxic activity of tripodal ferrocenyl bis-naphthalimide derivatives.

A series of tripodal ferrocenyl bis-naphthalimide derivatives were synthesized and characterized. All of the bis-naphthalimide derivatives exhibited good DNA binding ability which was confirmed by ethidium bromide (EB) displacement experiment and ultraviolet (UV)-visible absorption titration. And the binding mode of these compounds was proved to be a hybrid binding mode by experiments. The cytotoxicity of synthesized compounds against 4 different human cancer cell lines (EC109, BGC823, SGC7901 and HEPG2) was evaluated by thiazolyl blue tetrazolium bromide (MTT) assay. All of the bis-naphthalimide derivatives exhibited good anticancer activity than the positive control drug (amonafide), which was due to the promotion of reactive oxygen species (ROS) level in test cancer cells by the reversible one-electron redox process of ferrocenyl bis-naphthalimide derivatives. Although there was no obvious relationship between the binding constants and the chain length, the structure cytotoxicity relationship revealed that the linker of n = 3, m = 1 was the best choice for the tested tripodol bis-naphthalimide derivatives. SYNOPSIS: A series of tripodal ferrocenyl bis-naphthalimide derivatives were synthesized to study the DNA binding ability and the cytotoxicity induced by reactive oxygen species. All of the compounds exhibited good DNA binding ability. And the structure cytotoxicity relationship revealed that the structure of 5h was the best choice.

A new Schiff base copper (II) complex derived from estrone and d-glucosamine: Synthesis, characterization and its interaction with DNA.

A novel copper (II) complex of Schiff base prepared through condensation between 2-formyl-17-deoxyestrone and d-glucosamine was synthesized and characterized. Fluorescence spectroscopy was conducted to assess their binding ability with CT-DNA. The results showed that the copper (II) complex could bind to DNA with a weak intercalative mode. The interaction between the copper (II) complex and DNA was also investigated by gel electrophoresis. Interestingly, we found that the complex could cleave plasmid DNA (pUC19) to nicked and linear forms through an oxidative mechanism without the use of exogenous agents.

Highly enantioselective hetero- Diels-Alder reaction of trans-1-methoxy- 2-methyl-3-trimethylsiloxybuta-1,3-diene with aromatic and aliphatic aldehydes catalyzed by 3-substituted BINOL-titanium complex.

3-diphenylhydroxymethyl-substituted BINOL-titanium complex prepared in situ was found to be a highly efficient catalyst for hetero-Diels-Alder reaction of diene 1 with both aromatic and aliphatic aldehydes to give 2,5-disubstituted dihydropyrone in up to 99% yield and 99% ee.

Synthesis, DNA binding and cleavage activities of the copper (II) complexes of estrogen-macrocyclic polyamine conjugates.

A series of the copper (II) complexes 5a-d of estrogen-macrocyclic polyamine conjugates were synthesized and characterized. The interactions of complexes 5a-d with DNA were studied by fluorescence spectroscopy and gel electrophoresis under physiological conditions. The results indicate that the conjugated estrogens have increased the cleavage efficiency of Cu[cyclen](2+) while the conjugates display poor binding affinities. The functional groups of D-ring of estrogens may play a key role in deciding binding and cleavage extent of the complexes to DNA.

Synthesis, Characterization, DNA Interaction, and Antitumor Activities of La (III) Complex with Schiff Base Ligand Derived from Kaempferol and Diethylenetriamine.

A novel La (III) complex, [LaL(H2O)3]NO3 ·3H2O, with Schiff base ligand L derived from kaempferol and diethylenetriamine, has been synthesized and characterized by elemental analysis, IR, UV-visible, (1)H NMR, thermogravimetric analysis, and molar conductance measurements. The fluorescence spectra, circular dichroism spectra, and viscosity measurements and gel electrophoresis experiments indicated that the ligand L and La (III) complex could bind to CT-DNA presumably via intercalative mode and the La (III) complex showed a stronger ability to bind and cleave DNA than the ligand L alone. The binding constants (K b ) were evaluated from fluorescence data and the values ranged from 0.454 to 0.659 × 10(5) L mol(-1) and 1.71 to 17.3 × 10(5) L mol(-1) for the ligand L and La (III) complex, respectively, in the temperature range of 298-310 K. It was also found that the fluorescence quenching mechanism of EB-DNA by ligand L and La (III) complex was a static quenching process. In comparison to free ligand L, La (III) complex exhibited enhanced cytotoxic activities against tested tumor cell lines HL-60 and HepG-2, which may correlate with the enhanced DNA binding and cleaving abilities of the La (III) complex.