Wei-Yong Liu

Synthesis and discovery of pyrazole-5-carbohydrazide N-glycosides as inducer of autophagy in A549 lung cancer cells

A series of novel 3-aryl-1-arylmethyl-1H-pyrazole-5-carbohydrazide N-beta-glycoside derivatives was synthesized by the reaction of substituted 1H-pyrazole-5-carbohydrazide with d-sugar and the effects of all the compounds on A549 cell growth were investigated. The results showed that all compounds had inhibitory effects on the growth of A549 lung cancer cells and compound 3d possessed the highest growth inhibitory effect and induced autophagy of A549 lung cancer cells.

A rhodamine chromene-based turn-on fluorescence probe for selectively imaging Cu2+ in living cell

We describe the development of a rhodamine chromene-based turn-on fluorescence probe to monitor the intracellular Cu(2+) level in living cells. The new fluorescent probe with a chlorine group in chromene moiety exhibits good membrane-permeable property than previous reported because the predicted lipophilicity of present probe 4 is stronger than that of methoxyl substituted probe in our previous work (CLogP of 4: 8.313, CLogP of methoxyl substituted probe: 7.706), and a fluorescence response toward Cu(2+) under physiological conditions with high sensitivity and selectivity, and facilitates naked-eye detection of Cu(2+). The fluorescence intensity was remarkably increased upon the addition of Cu(2+) within 1 or 2 min, while the other sixteen metal ions caused no significant effect.

Synthesis of novel ribavirin hydrazone derivatives and anti-proliferative activity against A549 lung cancer cells.

A series of novel ribavirin hydrazone derivatives were synthesized by the reaction of ribavirin hydrazone with benzaldehyde or acetophenone derivatives. The structures of the compounds were determined by IR, (1)H NMR, and HRESIMS. Preliminary biological evaluation showed that one compound (7h) inhibits the growth of A549 cells at 20microM.

Fluorescence turn-on chemodosimeter for rapid detection of mercury (II) ions in aqueous solution and blood from mice with toxicosis.

The heavy metal mercury (Hg) is a threat to the health of people and wildlife in many environments. Among various chemical forms, Hg(2+) salts are usually more toxic than their counterparts because of their greater solubility in water; thus, they are more readily absorbed from the gastrointestinal tract into circulation. Therefore, new chemical receptors for detecting Hg(2+) ions in circulation are needed. In this study, we developed a rhodamine-based turn-on fluorescence probe to monitor Hg(2+) in aqueous solution and in blood of mice with toxicosis. The chemodosimeter responds to Hg(2+) ions stoichiometrically, rapidly, and irreversibly at room temperature as a result of a chemical reaction that produces strongly fluorescent oxadiazole. The new fluorescent probe shows good fluorescence response, with high sensitivity and selectivity, toward Hg(2+) ions in aqueous solution and in blood from mice with toxicosis and facilitates the naked-eye detection of Hg(2+) ions.

Phosphorylation and nuclear translocation of integrin β4 induced by a chemical small molecule contribute to apoptosis in vascular endothelial cells

Integrin β4 and its Y-1494 phosphorylation play an important role in cell signaling. We found a small molecule, ethyl1-(3-(4-chlorophenoxy)-2-hydroxypropyl)-3-(4-chlorophenyl)-1H-pyrazole-5-carboxylate (ECPC), that could elevate the levels of KIT ligand (KITLG), interleukin 8 (IL-8), prostaglandin-endoperoxide synthase 2 (PTGS2) and activating transcription factor 3 (ATF3) and promote apoptosis in vascular endothelial cells (VECs) through integrin β4. We investigated the underlying mechanism of integrin β4 participating in this process. ECPC treatment increased the phosphorylation of Y-1494 in the integrin β4 cytoplasmic domain via a well-known receptor tyrosine kinase, fibroblast growth factor receptor 1 (FGFR1), and integrin β4 translocated from the cytoplasm to nucleus. With suppression of Y-1494 phosphorylation by FGF-2 or siRNA of FGFR1, ECPC failed to promote integrin β4 nuclear translocation and could not increase the expression of KITLG, IL-8, PTGS2 or ATF3. Y-1494 phosphorylation and nuclear translocation of integrin β4 may be important during ECPC-induced apoptosis in VECs.

Novel ferrocenyl derivatives exert anti-cancer effect in human lung cancer cells in vitro via inducing G1-phase arrest and senescence

Aim:To investigate the effects of 7 novel 1-ferrocenyl-2-(5-phenyl-1H-1,2,4-triazol-3-ylthio) ethanone derivatives on human lung cancer cells in vitro and to determine the mechanisms of action.Methods:A549 human lung cancer cells were examined. Cell viability was analyzed with MTT assay. Cell apoptosis and senescence were examined using Hoechst 33258 and senescence-associated-β-galactosidase (SA-β-gal) staining, respectively. LDH release was measured using a detection kit. Cell cycle was analyzed using a flow cytometer. Intracellular ROS level was measured with the 2′,7′-dichlorodihydrofluorescein probe. Phosphorylation of p38 was determined using Western blot.Results:Compounds 5b, 5d, and 5e (40 and 80 μmol/L) caused significant decrease of A549 cell viability, while other 4 compounds had no effect on the cells. Compounds 5b, 5d, and 5e (80 μmol/L) induced G1-phase arrest (increased the G1 population by 22.6%, 24.23%, and 26.53%, respectively), and markedly increased SA-β-gal-positive cells. However, the compounds did not cause nuclear DNA fragmentation and chromatin condensation in A549 cells. Nor did they affect the release of LDH from the cells. The compounds significantly elevated the intracellular ROS level, decreased the mitochondrial membrane potential, and increased p38 phosphorylation in the cells. In the presence of the antioxidant and free radical scavenger N-acetyl-L-cysteine (10 mmol/L), above effects of compounds 5b, 5d, and 5e were abolished.Conclusion:The compounds 5b, 5d, and 5e cause neither apoptosis nor necrosis of A549 cells, but exert anti-cancer effect via inducing G1-phase arrest and senescence through ROS/p38 MAP-kinase pathway.

The synthesis, X-ray crystal structure and optical properties of novel 1-ferrocenyl-2-(3-phenyl-1H-1,2,4-triazol-5-ylthio)ethanone derivatives.

A series of novel 1-ferrocenyl-2-(3-phenyl-1H-1,2,4-triazol-5-ylthio)ethanone derivatives was synthesized by the reaction of 3-substituted-1H-1,2,4-triazole-5-thiol and chloroacetyl ferrocene in the presence of sodium hydride and potassium iodide at reflux. The structures of the new compounds were determined by IR and (1)H NMR spectroscopy and HRMS. The structure of compound 5c was established by X-ray crystallography. UV-vis absorption and fluorescence spectra were recorded in ethanol and dichloromethane. The results showed that compounds 5a-g display similar absorptions ranging from 300 to 500nm and maximal emission bands are about 566nm. The intensity of fluorescence and maximal emission bands are dependent on the groups bonded to triazole rings.

Synthesis, X-Ray Crystal Structures and Optical Properties of Novel Substituted Pyrazoly 1,3,4-Oxadiazole Derivatives

Novel pyrazoly 1,3,4-oxadiazole derivatives were synthesized and characterized by 1H NMR, IR, HRMS and X-ray diffraction analysis. UV–vis absorption and fluorescence properties of these compounds in different solutions showed that the maximum absorption wavelength was not significantly changed in different solvents; however, maximal emission wavelength was red-shifted with the increase of solvent polarity. Absorption λmax and emission λmax was less correlated with substituent groups on aryl rings.

2-[5-(1,3-Benzodioxol-5-yl)-3-ferrocenyl-4,5-dihydro-1H-pyrazol-1-yl]-4-phenyl-1,3-thia-zole.

In the title compound, [Fe(C5H5)(C24H18N3O2S)], the pyrazoline ring adopts a twist conformation. The thiazole ring forms dihedral angles of 83.7 (2) and 34.4 (2)° with the benzene ring of the benzodioxole ring and the fused phenyl ring, respectively. The molecular conformation is stabilized by an intramolecular C—H⋯π interaction. The crystal packing features intermolecular C—H⋯N, C—H⋯O hydrogen bonds and weak C—H⋯π interactions.

Synthesis, Structure Characterization, and X-ray Crystallography of Novel 1-Benzyl-3-phenyl-1H-pyrazole-5-carboxylate Derivatives with a Carbohydrate Moiety

A series of novel (2S,3R,4S,5R)-3,4,5-triacetoxy-tetrahydro-2H-pyran-2-yl 1-benzyl-3-phenyl-1H-pyrazole-5-carboxylate derivatives (3) were synthesized by the reaction of 2,3,4-tri-O-acetyl-α-D-xylopyranosyl bromide (2) and 1-benzyl-3-phenyl-1H-pyrazole-5-carboxylic acid (1) in the presence of sodium bicarbonate and tetrabutylammonium bromide in dichloromethane at reflux temperature. The structures of new compounds were determined by IR and 1H NMR spectroscopy and HR mass spectrometry (HRMS), and the configuration of the newly generated chiral carbon (C-1) in the xylose ring was tentatively assigned based on the X-ray crystallographic structure of 3d and 3g.