Design, synthesis and anticancer activity of naphthoquinone derivatives.

Basis on molecular docking and pharmacophore analysis of naphthoquinone moiety, a total of 23 compounds were designed and synthesised. With the help of reverse targets searching, anti-cancer activity was preliminarily evaluated, most of them are effective against some tumour cells, especially compound 12: 1-(5,8-dihydroxy-1,4-dioxo-1,4-dihydronaphthalen-2-yl)-4-methylpent-3-en-1-yl-4-oxo-4-((4-phenoxyphenyl)amino) butanoate whose IC50 against SGC-7901 was 4.1 ± 2.6 µM. Meanwhile the anticancer mechanism of compound 12 had been investigated by AnnexinV/PI staining, immunofluorescence, Western blot assay and molecular docking. The results indicated that this compound might induce cell apoptosis and cell autophagy through regulating the PI3K signal pathway.

Binding patterns and structure-activity relationship of CDK8 inhibitors.

A major goal of medicinal chemists is to identify and validate novel and effective kinase targets for treatment of cancer. Recent studies have shown that cyclin-dependent kinase 8 (CDK8) is a target for treatment of colorectal, breast, melanoma, and prostate cancers. The crystal structure of CDK8 has been reported, and eutectic interactions have been identified for 24 compounds that target CDK8. To more effectively develop CDK8 inhibitors, particularly those with improved selectivity, we summarized the structure, structure-activity relationships, and binding information of typical CDK8 inhibitors, which may serve as a reference for development of novel CDK8 inhibitors.

Determination of nitrofuran metabolites in shrimp by high performance liquid chromatography with fluorescence detection and liquid chromatography-tandem mass spectrometry using a new derivatization reagent.

A high performance liquid chromatography with fluorescence detection (HPLC-FLD) method for the simultaneous determination of total nitrofuran metabolite residues (furazolidone, furaltadone, nitrofurantoin, and nitrofurazone) in shrimp was developed. The method involves the acid hydrolysis of protein-bound metabolites, followed by the derivatization of the freed metabolites with the new fluorescent derivatization reagent 2-hydroxy-1-naphthaldehyde (HN) and subsequent liquid-liquid extraction (LLE). Separation is achieved on a YMC-Pack Polymer C18 column under alkaline conditions, and the high fluorescence intensity of the derivatives at an emission wavelength Em=463nm (Ex=395nm) enables, for the first time, their simultaneous determination in shrimp at concentrations as low as 1µg/kg by HPLC-FLD. The method was validated using blank shrimp fortified with all four metabolites at 0.5, 1.0 and 2.0µg/kg. Recoveries were >87% with relative standard deviations of <8.1% for all four metabolites. Furthermore, the results obtained by HPLC-FLD were in very good agreement with those obtained by LC-MS/MS analysis.

High-performance liquid chromatography with fluorescence detection for the determination of nitrofuran metabolites in pork muscle.

A simple and sensitive HPLC method with fluorescence detection (HPLC-FLD) is reported for the simultaneous determination of metabolites of four nitrofuran drugs (furazolidone, furaltadone, nitrofurantoin and nitrofurazone) in pork muscle. The method involves acid hydrolysis of the protein-bound drug metabolites and the conjugation of the released side-chains with a novel fluorescence agent 2-hydroxy-1-naphthaldehyde. After liquid-liquid extraction and effective separation of the derivatives on a YMC-Pack Polymer C18 column at 40°C under alkaline conditions, the high fluorescence intensity of these derivatives at emission wavelength λem = 463 nm enables their simultaneous determination in pork muscle at concentrations as low as 1 µg kg⁻¹. The method was validated using blank pork muscle fortified with all four metabolites at 0.5, 1.0 and 2.0 µg kg⁻¹. Recoveries were > 92.3% with RSDs < 8.5% for all four metabolites. The results obtained with HPLC-FLD and LC-MS/MS methods showed very good agreement for pork muscle samples.

(E)-2-[(2-Chloro-benzyl-idene)amino]-isoindoline-1,3-dione.

The title compound, C(15)H(9)ClN(2)O(2), adopts an E configuration about the C=N double bond. The mean plane of the isoindoline ring system [maximum deviation = 0.011 (2) Å] is inclined to the chloro-benzene ring by 22.62 (8)°. In the crystal, mol-ecules are connected by C-H⋯O hydrogen bonds, forming chains that propagate along [010].

N-(2,4-Dinitro-phen-yl)-1,3-dimeth-oxy-isoindolin-2-amine.

In the title compound, C(16)H(16)N(4)O(6), the planes of the isoindole and dinitro-benzene groups make a dihedral angle between of 84.15 (8)°. The N atom of the isoindole group is displaced by 0.2937 (3) Šfrom the plane through the remaining atoms. An intra-molecular N-H⋯O inter-action occurs. In the crystal, inversion dimers linked by pairs of N-H⋯O hydrogen bonds occur.

(E)-3-[(2-Hy-droxy-naphthalen-1-yl)methyl-idene-amino]-5-(morpholin-4-yl-meth-yl)-1,3-oxazolidin-2-one.

The title compound, C(19)H(21)N(3)O(4), crystallizes with two independent mol-ecules in the asymmetric unit. In both mol-ecules, there is an intra-molecular O-H⋯N hydrogen bond, which correlates with the fact that each mol-ecule adopts an E configuration with respect to the C=N bond. In the crystal, there are C-H⋯O and C-H⋯π inter-actions present.

(E)-1-[(2-Hy-droxy-1-naphth-yl)methyl-idene-amino]-imidazolidine-2,4-dione.

The title compound, C(14)H(11)N(3)O(3), adopts an E or trans configuration with respect to the C=N bond. In the mol-ecule there is an intra-molecular O-H⋯N hydrogen bond involving the hy-droxy substituent at the 2-positon of the naphthalene ring and the adjacent methyl-ene-amino N atom. The mol-ecule is roughly planar, the dihedral angle between the naphthalene and imidazolidine-2,4-dione mean planes being 8.4 (1)°. In the crystal, pairs of N-H⋯O hydrogen bonds link mol-ecules into inversion dimers. These dimers are futher linked via C-H⋯O inter-actions, forming a three-dimensional network.

Methyl 3-[(E)-(2-hy-droxy-1-naphth-yl)methyl-idene]carbazate.

The title compound, C(13)H(12)N(2)O(3), has an E configuration with respect to the C=N bond: the conformation is stabilized by an intramolecular O-H⋯N hydrogen bond. In the crystal, an N-H⋯O interaction links the molecules into a C(4) chain along [100].

(E)-N'-(3-Fluoro-benzyl-idene)-2-hydroxy-benzohydrazide.

The title compound, C(14)H(11)FN(2)O(2), adopts an E or trans configuration with respect to the C=N bond. An intra-molecular N-H⋯O hydrogen bond contributes to the relatively planarity of the mol-ecular conformation; the two benzene rings are inclined to one another by 12.5 (2)°. In the crystal structure, inter-molecular O-H⋯O hydrogen bonds link the mol-ecules into chains running parallel to the c axis.

(E)-2-Hydroxy-naphthalene-1-carb-al-de-hyde semicarbazone.

The title compound, C(12)H(11)N(3)O(2), adopts an E or trans configuration with respect to the C=N bond. There is an intra-molecular O-H⋯N hydrogen bond involving the hydroxyl H atom and an N atom of the hydrazine group. In the crystal structure, mol-ecules are connected via N-H⋯O hydrogen bonds, forming a three-dimensional network.

[Study on the interaction between BSA and nicotine].

The interaction of BSA and NIC was investigated by absorption spectra, fluorescence spectroscopy and synchronous fluorescence spectroscopy. In the system of sodium phosphate dibasic-citric acid of 0.1 mol(-1) x L(-1), fluorescence titration showed that the fluorescence intensity of BSA at 342 nm was quenched when NIC was added, NIC was capable of binding with BSA to form a 1:1 complex and the quenching mechanism of BSA affected by NIC was shown to be a static quenching procedure by calculating the binding number n and binding constant K. NIC decreased the intensity of the characteristic absorption peak of BSA, showing that the binding of NIC to BSA had strong impact on protein conformation with the decrease in a-helical content of the protein. Synchronous fluorescence indicated that the binding of NIC to BSA is near tryptophan subunit.

[Spectroscopic characterization of structure of cerium incorporated MCM-48 mesoporous molecular sieve].

Cerium incorporated MCM-48 molecular sieves have been hydrothermally synthesized using a mixed template and pH adjusting route. The samples were characterized by various physicochemical methods, including X-ray diffraction, diffuse reflectance UV-Vis spectroscopy, FTIR spectroscopy, XRF spectroscopy, and nitrogen adsorption. These results reveal that cerium is incorporated in MCM-48 and it is in the form of well-dispersed tetra-coodinated cerium ion. The proper concentration of cerium and adjusting pH can keep Ce-MCM-48 with higher specific surface area , larger unit-cell parameter, narrower pore-size distribution, and thicker pore wall than those of MCM-48. These deduce higher activity, and better selectivity, thermal stability and hydrothermal stability than those of MCM-48. The concentration of Ce incorporated in MCM-48 affects the vibration of the framewoke Si of molecular sieves.

[Fluorescence study on the interaction of salicylic acid and bovine serum albumin].

The interaction between salicylic acid and bovine serum albumin has been studied by fluorescence spectroscopy. The results show that the quenching mechanism of the combination of bovine serum albumin with salicylic acid is a static quenching procedure, the quenching constant K(sv) is 1.097 x 10(4) (mol x L(-1))(-1), and the equilibrium constant is 7.377 x 10(4). The number of binding sites is 1 and it is a strong one. When the ratio of molar concentration of salicylic acid to bovine serum albumin is lower than 1:1, it binds to Trp residue first but it doesn't result in any microenvironment changes of Trp residue. The binding distance between salicylic acid and bovine serum albumin and the energy transfer efficiency were obtained based on the theory of Förester spectroscopy energy transfer.