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Wang B.,Shanghai University | Wang B.,Shandong Institute of Pharmaceutical Industry | Ji S.,Hospital of PLA | Zhang H.,Shanghai University | And 5 more authors.
Steroids | Year: 2013

A rapid, simple and sensitive high-performance liquid chromatography tandem mass spectrometry method was developed and validated for simultaneous determination of six main steroidal saponins in Paris polyphylla in rat plasma. Ginsenoside Rg3 was selected as the internal standard (IS). Plasma samples were pretreated with protein precipitation, and the separation was achieved on a reverse phase Agilent poroshell120 EC-C18 column using a gradient mobile phase system of acetonitrile-water containing 0.1% formic acid. The triple quadruple mass spectrometer was set in negative electrospray ionization mode and multiple reaction monitoring (MRM) was used for six steroidal saponins quantification. The precursors to produce ion transitions monitored for polyphyllin I, polyphyllin II, polyphyllin VI, polyphyllin VII, dioscin, gracillin and IS were m/z 899.5 > 853.4, 1059.5 > 1013.5, 783.4 > 737.4, 1075.5 > 1029.5, 913.5 > 867.4, 929.5 > 883.4 and 819.5 > 783.4, respectively. The intra- and inter-day precisions (RSD%) were less than 13% and the average extraction recoveries ranged from 85% to 97.0% for each analyte. Six steroidal saponins were proved to be stable during sample storage, preparation and analytical procedures. The established method was employed for simultaneous quantification and successfully used for the first time for the pharmacokinetics evaluation of the six main compounds after intragastric administration of P. polyphylla extract in Sprague-Dawley rats. © 2013 Elsevier Ltd. All rights reserved.


Zhu R.-X.,Key Laboratory of Colloid and Interface Chemistry | Zhang D.-J.,Key Laboratory of Colloid and Interface Chemistry | Guo J.-X.,Key Laboratory of Colloid and Interface Chemistry | Mu J.-L.,Key Laboratory of Colloid and Interface Chemistry | And 2 more authors.
Journal of Physical Chemistry A | Year: 2010

A computational study with the B3LYP density functional theory was carried out to study the reaction mechanism for the cycloisomerization of allenes catalyzed by Au(I) and Au(III) complexes. The catalytic performance of Au complexes in different oxidation states as well as the effects of the counterion on the catalytic activities has been studied in detail. Our calculations show that the catalytic reaction is initiated by coordination of the Au(I) or Au(III) catalyst to the distal double bond of allene and activation of allene toward facile nucleophilic attack, then 3-pyrroline obtained via two-step proton shift, followed by demetalation. On the basis of our calculations, H shifts are key steps of the catalytic cycle, which are significantly affected by the gold oxidation state, counterion, ligands, and assistant catalyst. AuCl is found to be more reactive than AuCl3; however, the Au(III)-catalyzed path does not involve an oxidation state change from Au(III) to Au(I). Our calculated results rationalize the experimental findings well and overthrow the previous conjecture about Au(I) serving as the catalytically active species for Au(III)-catalyzed cycloisomerization. © 2010 American Chemical Society.


Jia Y.,Shandong Institute of Pharmaceutical Industry | Zhang J.,Shandong University | Feng J.,Shandong Academy of Sciences | Xu F.,Shandong University | And 2 more authors.
Chemical Biology and Drug Design | Year: 2014

A novel series of pazopanib derivatives were designed, synthesized, and evaluated for their inhibitory activity against a series of kinases including VEGFR-2, EGFR, AKT1, ALK1, and ABL1. The anti-angiogenic activities ex vivo of some compounds were also investigated. Compounds P2d and P2e demonstrated outstanding inhibitory activity against VEGFR-2 and ABL1 and higher anti-angiogenic activity compared with Pazopanib, the reference standard. These two compounds (P2d and P2e) could be used as novel lead compounds for further development of anticancer agents. © 2013 John Wiley & Sons A/S.


Zhang Y.,Shandong University | Liu C.,Shandong University | Chou C.J.,Medical University of South Carolina | Wang X.,Postdoctoral Workstation | And 2 more authors.
Chemical Biology and Drug Design | Year: 2013

In our previous study, we developed a novel series of tetrahydroisoquinoline-based hydroxamic acid derivatives as histone deacetylase inhibitors (Bioorg Med Chem, 2010, 18, 1761-1772; J Med Chem, 2011, 54, 2823-2838), among which, compound ZYJ-34c (1) was identified and validated as the most potent one with marked in vitro and in vivo antitumor potency (J Med Chem, 2011, 54, 5532-5539.). Herein, further modification in 1 afforded another oral active analog ZYJ-34v (2) with simplified structure and lower molecular weight. Biological evaluation of compound 2 showed efficacious inhibition against histone deacetylase 1, 2, 3, and 6, which was confirmed by Western blot analysis results. Most importantly, compound 2 exhibited similar even more potent in vitro and in vivo antitumor activities relative to the approved histone deacetylase inhibitor SAHA. Structural modification of 1 led to another oral active HDACi 2 with simplified structure and lower molecular weight. Compared with the approved HDACi SAHA, 2 exhibited similar even superior in vitro and in vivo antitumor potency.© 2013 John Wiley and Sons A/S.


Ma Y.,Shenyang Pharmaceutical University | Ma Y.,Shandong Institute of Pharmaceutical Industry | Li Y.,Zhangqiu Peoples Hospital | Li X.,Shandong Hongjitang Pharmaceutical Group Co. | Wu Y.,Shenyang Pharmaceutical University
International Journal of Molecular Sciences | Year: 2013

The present study evaluated the anti-inflammatory effects of 4-methylcyclopentadecanone (4-MCPC) on edema models in mice and aimed to determine the safety of 4-MCPC after acute exposure. The acute toxicity of 4-MCPC was evaluated by oral administration to rats of single doses of 0, 5, 50, 500 and 5000 mg/kg. Toxic symptoms were observed for 14 days. The anti-inflammatory activity was evaluated in xylene-induced mouse ear edema and carrageenan-induced mouse paw edema. The animals were treated with 4-MCPC once every day for seven consecutive days. Edema index, % inhibition, IL-1β, TNF-α, PGE2 and MPO levels in paws were detected after the treatment with xylene or carrageenan. Our results indicated that the LD50 value of 4-MCPC in rats is greater than 5000 mg/kg. The ED50 of 4-MCPC in xylene-induced mouse ear edema model was 7.5 mg/kg. 4MCPC (8 or 16 mg/kg) remarkably inhibited carrageeninduced mouse paw edema. Further study revealed that 4-MCPC treatment also decreased IL-1β, TNF-α, PGE2 and MPO levels in mice paws. Intragastric administration- MfCP C exhibited more significant anti-inflammatory activity than muscone at a dose of 16 mg/kg. Taken together, our results suggest that 4-MCPC has potent anti-inflammatory activity and the mechanisms might be related to the decreases of the levels of IL-1β, TNF-α, PGE2 and MPO in inflamed paws.© 2013 by the authors; licensee MDPI, Basel, Switzerland.


Han G.,Shandong University | Han G.,Institute of Biopharmaceuticals of Shandong Province | Han G.,Liaoning Medical University | Wang G.,Shandong University | And 10 more authors.
Carbohydrate Polymers | Year: 2012

This study was conducted to evaluate the protective effect of intra-articular (IA) injection of xanthan gum (XG) on articular cartilage in the papain-induced osteoarthritis (OA) model. The purified XG and injection were prepared and their qualities were evaluated. The rabbit knee OA model was induced through IA injection of papain and the protective effect on articular cartilage was evaluated through recording the width of knee joint, performing the morphological observation and histological evaluation of articular cartilage and synovium, measuring the sulphated glycosaminoglycans (GAGs) in cartilage. Our results showed that XG injection was of high transparency, low protein and endotoxin-free. IA injection of XG could protect the joint cartilage and this was probably an effective therapeutic method of OA. © 2011 Elsevier Ltd. All rights reserved.


Lv P.-L.,Shandong University | Zhu R.-X.,Shandong University | Zhang D.-J.,Shandong University | Duan C.-G.,Shandong Institute of Pharmaceutical Industry | Liu C.-B.,Shandong University
Journal of Physical Chemistry A | Year: 2012

The asymmetric epoxidation of 2-cyclohexen-1-one with aqueous H 2O 2 as oxidant, 1,2-diaminocyclohexane as catalyst, and a Brønsted acid trifluoroacetic acid (TFA) as cocatalyst has been studied by performing density functional theory calculations. It is confirmed that the catalyzed epoxidation proceeds via sequential nucleophilic addition and ring-closure processes involving a ketiminium intermediate. Four possible pathways associated with two Z isomers and two E isomers of ketiminium have been explored in detail. Our calculation indicates that these four pathways have high barriers and a small energy gap between two more favorable R and S pathways. We have analyzed the effects of the TFA anion and H 2O on the activity and enantioselectivity of catalytic epoxidation. It is found that the TFA anion acts as a counterion to stabilize the transition states of the catalytic epoxidation by hydrogen-bond acceptance, leading to decreases in the barriers of the nucleophilic addition and ring-closure processes. The most significant decrease occurred in the ring-closure step of the Z-R-pathway, resulting in H-bond-induced enantioselectivity. Our calculations also show that water cooperates with TFA to further increase the reaction rate significantly. © 2011 American Chemical Society.


Chen X.-Y.,Shandong Institute of Pharmaceutical Industry | Shi H.-Y.,Shandong Institute of Pharmaceutical Industry | Zhao A.-L.,Shandong Institute of Pharmaceutical Industry
Chinese Journal of New Drugs | Year: 2013

Objective: To investigate the formulation and technology of ergoloid mesylate sustained-release tablets, and evaluate their quality in vitro. Methods: The dissolution profiles of the product were fitted by Peppas equation. By means of mean dissolution time (MDT) of drug and the similarity factor (f2), the optimal formulation was determined by orthogonal test and its repeatable experiment was done. The effects of compression force and granulation method on dissolution behavior were investigated. Results: Carbomer played a key role and tartaric acid a promoting role in dissolution behavior. The compression force within a certain range had no remarkable effect on the dissolution profiles, but the granulation method had an influence on dissolution rate. The optimal formulation was repeatable. The dissolution profiles of final product were similar to those of the marked preparation (control). Conclusion: Ergoloid mesylate sustained-release tablets have been produced successfully, and the formulation and technology are suitable for the industrial production.


PubMed | Shandong Institute of Pharmaceutical Industry
Type: Journal Article | Journal: Chemical biology & drug design | Year: 2014

A novel series of pazopanib derivatives were designed, synthesized, and evaluated for their inhibitory activity against a series of kinases including VEGFR-2, EGFR, AKT1, ALK1, and ABL1. The anti-angiogenic activities ex vivo of some compounds were also investigated. Compounds P2d and P2e demonstrated outstanding inhibitory activity against VEGFR-2 and ABL1 and higher anti-angiogenic activity compared with Pazopanib, the reference standard. These two compounds (P2d and P2e) could be used as novel lead compounds for further development of anticancer agents.


Guo J.,Shandong University | Zhang D.,Shandong University | Duan C.,Shandong Institute of Pharmaceutical Industry | Liu C.,Shandong University
Carbohydrate Research | Year: 2010

The interactions of the cellulose molecule with several anions, including acetate , alkyl phosphate, tetrafluoroborate and hexafluorophosphate anions which are most commonly involved in the imidazolium ionic liquids (ILs), have been studied by performing density functional theory calculations. Based on calculated geometries, energies, IR characteristics, and electronic properties of the cellulose-anion complexes, it is found that the strength of interactions of anions with cellulose follows the order: acetate anion > alkyl phosphate anion > tetrafluoroborate anion > hexafluorophosphate anion, which is consistent with the experimentally observed solubility trend of cellulose in the corresponding imidazolium-based ILs. The present study may provide basic aids to some extent for understanding the dissolution behavior of cellulose in the imidazolium-based ILs. © 2010 Elsevier Ltd. All rights reserved.

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