Jiakun Xu

Proteasome inhibition and cytostatic effects on human cancer cells by pyrazolone-enamines: a combined crystallographic, structural and computational study

Nine compounds were designed and synthesized by the condensation reaction of the carbonyl in 4-benzoyl-3-methyl-1-phenyl-2-pyrazolin-5-one (HPMBP) with the amino groups in 5-aminoisophthalic acid, 4,4′-diaminodiphenylmethane, 4-aminophenylacetic acid, 4-aminobenzamide, 2-amino-4-methylphenol, 5-amino-2-methylphenol, 2-aminophenol, 3-aminophenol and 4-aminophenol. They were then characterized by IR, 1H NMR, elemental analysis, and X-ray crystallography, which suggested that all of them exist as the pyrazolone-enamine forms in the solid state and in a DMSO solution through tautomeric reactions. The nine compounds (compounds 1–9) were evaluated for their ability to inhibit the proliferation of human liver cancer HepG2 cells. Compounds 5, 6, 7 and 8 demonstrated a strong inhibitory effect on the proliferation of HepG2 cells. The nine compounds can also inhibit the activity of the human cancer cellular 20S proteasome. Further studies on compound 6 as the representative indicate that it can cause the accumulation of ubiquitinated proteins and the proteasome target proteins Bax and p27, and exhibit a cytostatic effect in HepG2 cells in a concentration-dependent and time-dependent manner. The four potential tautomers of compound 6 were optimized and their single point energies were calculated by the density functional theory (DFT) B3LYP method based on the polarized continuum model (PCM) in water to identify the most likely tautomer existing in cancer cells. Based on the optimized structure of the most stable tautomer in water, the Wiberg bond orders, molecular electrostatic potential (MEP) maps and frontier molecular orbital were calculated. As compounds 5, 6, 7 and 8 have hydroxyl in the ortho-position or meta-position, our study can provide some information to study their anticancer mechanism and the substitution effect of different functional groups.

Synthesis, Characterization, and Electrochemical Studies on the Interaction of Binuclear Cu(II) Complex with DNA

A new Schiff base ligand (KH 2 L) was synthesized using potassium salt of glycine and 2,4-dihydroxybenzaldehyde. A binuclear complex of this ligand [Cu 2 (HL) 2 ] 2H 2 O was synthesized and characterized by elemental analyses, IR, UV, TG-DTG, and molar conductance. The fundamental electrochemical characteristics of the Cu(II) complex have been studied, and the interaction of the copper complex and DNA was also studied by cyclic voltammetry and fluorescence spectra. The results of the cyclic voltammetry showed that the Cu(II) complex had an oxidation peak with the oxidation potential at −0.345 V. After the DNA was added, the peak current declined with the peak potential shifting positively. This suggested that the complex combined with DNA in the form of intercalative binding, which was also proved by the fluorescence analysis.

Crystal structure of 2-aminobenzothiazolinium nitrate and theoretical study of the amino-imino tautomerism of 2-aminobenzothiazole

Abstract 2-Aminobenzothiazolinium nitrate (1) was characterized by elemental analysis, melting point, IR, 1H NMR, and X-ray crystallography. The driving force for the 2-aminobenzothiazole tautomerism in methanol solution was studied using theoretical calculations. It is suggested that the 2-aminobenzothiazolinium cation is an intermediate product between the amino form (2) and imino form (3) of 2-aminobenzothiazole. The tautomerization reaction can proceed in two steps through protonation and deprotonation between the two forms 2 and 3.