Publications by authors named "Huahui Zeng"

20 Publications

  • Page 1 of 1

Preparation of Ti C T MXene based solid phase microextraction coating for sensitive determination of polychlorinated biphenyls in environmental water samples.

J Sep Sci 2021 Jul 15. Epub 2021 Jul 15.

Center for modern analysis and gene sequencing, Zhengzhou University, No 100 of Kexue Road, Zhengzhou, 450001, China.

In this study, a new Ti C T -coated fiber was synthesized and utilized as coatings for solid-phase microextraction of seven polychlorinated biphenyls. The as-produced multilayered Ti C T MXene was characterized by X-ray diffractometer, thermos-gravimetric analysis, scanning electron microscopy, and energy dispersive spectroscopy. It is noteworthy that the Ti C T showed some attractive features including unique 2D layered structures, large surface area, good hydrophilicity and rich active recognition sites, endowing it has a high affinity towards the target polychlorinated biphenyls. Subsequently, the affecting parameters on the extraction efficiency of polychlorinated biphenyls were optimized. Under the optimal conditions, a novel method for the analysis of polychlorinated biphenyls in water samples was proposed. The Ti C T -coated fiber based solid-phase microextraction method showed good linearity (r > 0.9928), high enrichment factors (268-442), low limits of detection (0.06-0.15 ng L ), and satisfactory repeatability (RSDs < 7.5%) for the PCBs. The excellent method recoveries were in the range of 90.0-98.4%, 92.0-98.2%, and 92.0-98.0% for river water, lake water, and tap water sample, respectively. These results suggested that the proposed Ti C T -coated fiber based method represents a promising alternative for the analysis of polychlorinated biphenyls. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/jssc.202100247DOI Listing
July 2021

Facile synthesis of magnetic sulfonated covalent organic framework composites for simultaneous dispersive solid-phase extraction and determination of β-agonists and fluoroquinolones in food samples.

Food Chem 2021 Mar 13;339:128079. Epub 2020 Sep 13.

Center of Advanced Analysis and Computational Science, Key Laboratory of Molecular Sensing and Harmful Substances Detection Technology, Zhengzhou University, Zhengzhou 450001, China.

In this work, an efficient method for the determination of β-agonists and fluoroquinolones was established, based on a mixed-mode sorbent of magnetic sulfonated covalent organic framework composites. By coupling with HPLC-MS/MS, the main factors that affect the extraction procedure were optimized. Under the optimal conditions, the proposed HPLC-MS/MS method was successfully utilized for the extraction of β-agonists and fluoroquinolones in milk and pork meat samples. The method showed good linearities (R ≥ 0.9916), and low LOQs of 0.1-0.2 ng g for β-agonists and fluoroquinolones. The adsorption mechanism was investigated with the assistance of quantum chemistry calculation method, and it is worth noting that the sorbent relied mainly on the multiple adsorption mechanisms, including π-π stacking, hydrophobic, electrostatic attraction and hydrogen-bonding interactions. This work not only provides a simple method for the preparation of a mixed-mode sorbent, but also a routine analysis strategy for monitoring the illegal use of β-agonists and fluoroquinolones.
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http://dx.doi.org/10.1016/j.foodchem.2020.128079DOI Listing
March 2021

antitumor effects of carboxymethyl chitosan-conjugated triptolide after oral administration.

Drug Deliv 2020 Dec;27(1):848-854

Academy of Chinese Medicine Sciences, Henan University of Chinese Medicine, Zhengzhou, China.

The purpose of this study is to evaluate antitumor efficacy and subacute toxicity of triptolide (TP) prodrug, a conjugate between TP and carboxymethyl chitosan (CC). The CCTP conjugate contained 4∼ wt % TP and displayed excellent aqueous solubility (5 mg/mL) as compared to the native TP (17 μg/mL). cytotoxicity of CCTP conjugate was evaluated by CCK8 assay against human pancreatic cancer (PC) cell lines, showing comparable the half maximal inhibitory concentration (IC) values to the parent TP. In a mouse model of PC (BxPC-3), the CCTP conjugate administered orally (at dose levels as low as 0.2 mg TP equivalent/kg) showed comparable efficacy in reducing or eliminating xenograft tumor to the same dose of TP, but exhibited much lower subacute toxicity as seen in body weight loss and hematological toxicity.
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http://dx.doi.org/10.1080/10717544.2020.1770370DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8216443PMC
December 2020

Dehydroabietic acid alleviates high fat diet-induced insulin resistance and hepatic steatosis through dual activation of PPAR-γ and PPAR-α.

Biomed Pharmacother 2020 Jul 12;127:110155. Epub 2020 May 12.

School of Life Sciences, Faculty of Science, University of Technology Sydney, PO Box 123, Broadway, NSW, 2007, Australia.

Dual-PPAR-α/γ agonist has the dual potentials to improve insulin resistance (IR) and hepatic steatosis associated with obesity. This study aimed to investigate whether dehydroabietic acid (DA), a naturally occurred compound, can bind to and activate both PPAR-γ and PPAR-α to ameliorate IR and hepatic steatosis in high-fat diet (HFD)-fed mice.. We found that DA formed stable hydrogen bonds with the ligand-binding domains of PPAR-γ and PPAR-α. DA treatment also promoted 3T3-L1 differentiation via PPAR-γ activation, and mitochondrial oxygen consumption in HL7702 cells via PPAR-α activation. In HFD-fed mice, DA treatment alleviated glucose intolerance and IR, and reduced hepatic steatosis, liver injury markers (ALT, AST), and lipid accumulation, and promoted mRNA expression of PPAR-γ and PPAR-α signaling elements involved in IR and lipid metabolism in vivo and in vitro, and inhibited mRNA expression of pro-inflammatory factors. Therefore, DA is a dual-PPAR-α/γ and PPAR-γ partial agonist, which can attenuate IR and hepatic steatosis induced by HFD-consumption in mice.
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http://dx.doi.org/10.1016/j.biopha.2020.110155DOI Listing
July 2020

Novel Carboxylated Chitosan-Based Triptolide Conjugate for the Treatment of Rheumatoid Arthritis.

Pharmaceutics 2020 Feb 26;12(3). Epub 2020 Feb 26.

Academy of Chinese Medicine Sciences, Henan University of Chinese Medicine, Zhengzhou 450046, China.

A new platform for triptolide (TP) delivery was prepared by conjugating TP to a carboxylmethyl chitosan (CMCS). Compared with the natural TP, the TP-conjugate (TP-CMCS) containing TP of ~5 wt% exhibited excellent aqueous solubility (> 5 mg/mL). Results of in vitro experiments showed that TP-CMCS could relieve TP-induced inhibition on RAW264.7 cells and apoptosis, respectively. Compared with the TP group, TP-CMCS could effectively alleviate the toxicity injury of TP and decreased the mortality rate of the mice (p < 0.05). TP-CMCS did not cause much damage to the liver (AST and ALT) and kidney (BUN and CRE) (p < 0.05). After administration, the levels of IL-6, IL-1β, and TNF-α decreased, and the arthritis detumescence percentages increased significantly, and the bony erosion degree was distinctly decreased in the TP-CMCS groups and TP group. Our results suggested that TP-CMCS was a useful carrier for the treatment of RA, which enhanced aqueous solubility of free TP and reduced drug toxicity in vitro and in vivo.
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http://dx.doi.org/10.3390/pharmaceutics12030202DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7150988PMC
February 2020

Magnolol alleviates Alzheimer's disease-like pathology in transgenic C. elegans by promoting microglia phagocytosis and the degradation of beta-amyloid through activation of PPAR-γ.

Biomed Pharmacother 2020 Apr 27;124:109886. Epub 2020 Jan 27.

Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou 450046, China. Electronic address:

This study aims to investigate whether magnolol (MG), a natural neolignane compound, can prevent AD induced by beta-amyloid (Aβ) and the possible mechanisms involved. MG dose-dependently reduces Aβ deposition, toxicity and memory impairment caused by Aβ in transgenic C. elegans. More importantly, these effects are reversed by GW9662, a selective peroxisome proliferator-activated receptor-γ (PPAR-γ) antagonist. MG is more effective in enhancing PPAR-γ luciferase levels than honokiol (HK). Meanwhile, MG has the potential to bind with the ligand binding domain of PPAR-γ (PPAR-γ-LBD). As expected, MG inhibited the luciferase activity of NF-κB and its target genes of inflammatory cytokines, and this effect was blocked by GW9662. The luciferase activity of Nrf2-ARE expression can be activated by MG and decreased Aβ-induced reactive oxygen species (ROS). The target gene LXR of PPAR-γ is activated by MG, which upregulates ApoE and promotes microglia phagocytosis and the degradation of Aβ, and these effects were also reversed by GW9662. In summary, MG can attenuate Aβ-induced AD and the underlying mechanism is the reduction of inflammation and promotion of phagocytosis and degradation of Aβ, which is dependent on PPAR-γ.
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http://dx.doi.org/10.1016/j.biopha.2020.109886DOI Listing
April 2020

Preparation of Progesterone Co-Crystals Based on Crystal Engineering Strategies.

Molecules 2019 Oct 31;24(21). Epub 2019 Oct 31.

Academy of Chinese Medicine, Henan University of Chinese Medicine, Zhengzhou 450046, Henan, China.

Three co-formers of 2-chloro-4-nitroaniline (CNA), 2,5-dihydroxybenzoic acid (DHB), and 4,4'-biphenol (DOD) were selected to prepare the co-crystal of progesterone (PROG) based on crystal engineering strategies. These co-crystals were successfully obtained via slow evaporation from different solutions and were characterized by single-crystal X-ray diffraction spectroscopy, powder X-ray diffraction, IR spectroscopy, and differential scanning calorimetry. Different binding networks were observed in the co-crystal structures of PROG. The PROG-CNA co-crystal had the fastest rates and highest concentrations of PROG in PBS solution compared with PROG or other co-crystals in the dissolution experiments. This might be attributable to more stable and abundant interactions between the PROG and CNA molecules. Our investigations provide positive support for the selection of suitable co-formers using crystal engineering strategies.
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http://dx.doi.org/10.3390/molecules24213936DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6864860PMC
October 2019

Composite host lattices of 4,4'-sulfonyldibenzoate water/boric acid in two tetrapropylammonium inclusion compounds.

Acta Crystallogr C Struct Chem 2018 09 21;74(Pt 9):1026-1031. Epub 2018 Aug 21.

Chemistry and Chemical Engineering Department, Northwest Normal University, Lanzhou, Gansu 730070, People's Republic of China.

Two novel inclusion compounds of 4,4'-sulfonyldibenzoate anions and tetrapropylammonium cations with different ancillary molecules of water and boric acid, namely bis(tetrapropylammonium) 4,4'-sulfonyldibenzoate dihydrate, 2CHN·CHOS·HO (1), and bis(tetrapropylammonium) 4,4'-sulfonyldibenzoate bis(boric acid), 2CHN·CHOS·2HBO (2), were prepared and characterized using single-crystal X-ray diffraction. In the two salts, the host 4,4'-sulfonyldibenzoic acid molecules, which are converted to the corresponding anions under basic conditions, can be regarded as proton acceptors which link different proton donors of the ancillary molecules of water or boric acid. In this way, an isolated hydrogen-bonded tetramer is constructed in salt 1 and a ribbon is constructed in salt 2. The tetramers and ribbons are then packed in a repeating manner to generate various host frameworks, and the tetrapropylammonium guest counter-ions are contained in the cavities of the host lattices to give the final stable crystal structures. In these two salts, although the host anion and guest cation are the same, the difference in the ancillary small molecules results in different structures, indicating the significance of ancillary molecules in the formation of crystal structures.
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http://dx.doi.org/10.1107/S2053229618011580DOI Listing
September 2018

Development of C-Labeled ω-sulfhydryl fatty acid tracer for myocardial imaging with PET.

Eur J Med Chem 2018 Jan 23;143:1657-1666. Epub 2017 Oct 23.

Department of Nuclear Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310009, China.

[C]-S-methyl-16-thiopalmitic acid (a) was developed with excellent heart-to-background uptake ratios and higher retention in heart. Myocardial uptake and metabolism of the tracer is markedly higher CPT I dependent. When compared to [C]-S-methyl-14-thiomyristic acid (b), [C]-S-methyl-12-thiododecanoic acid (c) and [C]-palmitate, a showed an early high uptake and a significantly slower late clearance in heart and a prolonged myocardial elimination half-life (30 min). Analysis of heart tissue and urine samples showed that a was metabolized via beta-oxidation in myocardium. Small animal PET images of the accumulation of a in the rat myocardium were clearly superior to [C]-palmitate. These initial studies suggest that a could be a potentially useful clinical PET tracer to assess myocardial fatty acid metabolism.
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http://dx.doi.org/10.1016/j.ejmech.2017.10.062DOI Listing
January 2018

[Cloning and sequence analysis of variable region genes of mouse anti-human S100A9 monoclonal antibody].

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2017 Feb;33(2):252-5

Objective: To clone and analyze variable region gene sequences of mouse monoclonal antibody against human S100A9( anti-human S100A9 mAb).

Methods: Total RNA was extracted from the hybridoma cell line( Ⅱ D4B10)secreting mouse anti-human S100A9 mAb. Furthermore,the heavy chain variable region( VH) and light chain variable region( VL) genes were amplified using reverse transcription-polymerase chain reaction( RT-PCR). After the cloning and sequencing of the VHand VLgenes,the sequence analyses were performed by BLAST program.

Results: The VLgene,a member of the mouse IGKV14-111* 01 family,had an open reading frame( ORF) of 291 bp with 97 amino acids,and the VHgene,a member of the mouse IGHV1-80* 01 family,had an ORF of 324 bp with 108 amino acids. In addition,the sequences of VH and VLgenes presented the characteristics of antibody variable region with individual frameworks and complementarity determining regions.

Conclusion: The variable region gene sequences of mouse anti-human S100A9 mAb have been successfully obtained,which are helpful to construct genetically engineered antibody in the future.
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February 2017

Synthesis and evaluation of [(18)F]-fluoromethyl triphenylphosphonium cation as a novel mitochondria-specific positron emission tomography tracer.

Eur J Med Chem 2016 Aug 20;118:90-7. Epub 2016 Apr 20.

Chinese Medicine Immunology Laboratory & Science and Technology Department, Henan University of Chinese Medicine, Jinshui East Road Boxue Road, Zhengzhou, 450046, China. Electronic address:

We developed a radiosynthesis of the voltage sensitive tracer [(18)F]-fluoromethyltriphenylphosphonium cation ([(18)F]-FTPMP), giving high yield (30-34%, decay-corrected), radiochemical purity (>99%) and specific activity (about 760 GBq/μmol). [(18)F]-FTPMP had suitable lipophilicity (logP = 0.91 ± 0.03) and high in vivo/vitro stability. Biodistribution studies showed that [(18)F]-FTPMP had high heart uptake (>7%ID/g from 10 min to 120 min postinjection) and rapid clearance from the background. Clear cardiac images were obtained at different time periods, and the infarction areas could be detected sensitively with small-animal PET. The autoradiography and myocardial membrane potential studies confirmed the mitochondria specific of [(18)F]-FTPMP in rat myocardia. These excellent pharmacokinetic properties suggest [(18)F]-FTPMP is a promising mitochondria-specific tracer for clinical PET imaging of myocardial diseases associated with mitochondrial dysfunction.
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http://dx.doi.org/10.1016/j.ejmech.2016.04.036DOI Listing
August 2016

Alzheimer's disease drug development based on Computer-Aided Drug Design.

Eur J Med Chem 2016 Oct 3;121:851-863. Epub 2015 Sep 3.

Science & Technology Department, Henan University of Traditional Chinese Medicine, Zhengzhou 450046, China. Electronic address:

Alzheimer's disease (AD) is a common neurodegenerative disorder characterized by the excessive deposition of amyloids in the brain. The pathological features mainly include the extracellular amyloid plaques and intracellular neurofibrillary tangles, which are the production of amyloid precursor protein (APP) processed by the α-, β- and γ-secretases. Based on the amyloid cascade hypotheses of AD, a large number of amyloid-β agents and secretase inhibitors against AD have been recently developed by using computational methods. This review article describes pathophysiology of AD and the structure of the Aβ plaques, β- and γ-secretases, and discusses the recent advances in the development of the amyloid agents for AD therapy and diagnosis by using Computer-Aided Drug Design approach.
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http://dx.doi.org/10.1016/j.ejmech.2015.08.039DOI Listing
October 2016

Synthesis and biological evaluation of fatty acids conjugates bearing cyclopentadienyl-donors incorporated [(99m)Tc/Re(CO)3]+ for myocardical imaging.

Eur J Med Chem 2014 Jan 22;72:10-7. Epub 2013 Nov 22.

Key Laboratory of Radiopharmaceuticals of Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, China. Electronic address:

Four (99m)Tc-labeled fatty acid analogs, 1b, 2b, 3b, 4b were synthesized by a double ligand transfer reaction and theirs potential were investigated. The radiochemical yield of the radiotracers was from 11.7% to 30.3% (no decay corrected). Those compounds were found to be chemically stable when incubated in SD rat serum for 3 h at 37 °C. The biodistribution studies in mice showed that high radioactivity accumulated of Tc-99m complexes were observed, followed by moderate clearance from the heart. The maximum heart/blood ratio was 5.7 at 15 min postinjection of 1b. Metabolite analysis showed 1b was not metabolized by β-oxidation in the heart. These results suggest that 1b may be a promising radiotracer for evaluation of myocardial viability.
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http://dx.doi.org/10.1016/j.ejmech.2013.11.015DOI Listing
January 2014

Preliminary studies of a novel cyclopentadienyl tricarbonyl technetium-99m fatty acid derivative for myocardical imaging.

J Labelled Comp Radiopharm 2013 Jan 7;56(1):1-5. Epub 2012 Dec 7.

Department of Nuclear Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China, 310009; Key Laboratory of Radiopharmaceuticals of Ministry of Education, College of Chemistry, Beijing Normal University, Beijing, China, 100875.

This study reports the synthesis and evaluation studies of 6'-cyclopentadienyl tricarbonyl technetium-99m 6'-oxo-11-(hexanamide)undecanoic acid (1). 1 was prepared with 26.5 ± 4.3% of radiochemical yield and more than 98% of radiochemical purity. Tissue distribution in mice showed that high radioactivity accumulated in the heart with moderate clearance. However, unfortunately, similar to those of other technetium-labeled fatty acid analogs, the biodistribution studies of 1 in mice showed poor heart-to-blood ratios, which suggested that 1 cannot be used as myocardial imaging agent, and it may provide a theoretical basis or a lab experience for corresponding fatty acid tracers studies.
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http://dx.doi.org/10.1002/jlcr.2987DOI Listing
January 2013

Novel pyrrolopyridinone derivatives as anticancer inhibitors towards Cdc7: QSAR studies based on dockings by solvation score approach.

Eur J Pharm Sci 2013 Nov 8;50(3-4):323-34. Epub 2013 Aug 8.

Pharmacy College, Henan University of Traditional Chinese Medicine, Zhengzhou 450046, China.

A series of pyrrolopyridinone derivatives as specific inhibitors towards the cell division cycle 7 (Cdc7) was taken into account, and the efficacy of these compounds was analyzed by QSAR and docking approaches to gain deeper insights into the interaction mechanism and ligands selectivity for Cdc7. By regression analysis the prediction models based on Grid score and Zou-GB/SA score were found, respectively with good quality of fits (r(2)=0.748, 0.951; r(cv)(2)=0.712, 0.839). The accuracy of the models was validated by test set and the deviation of the predicted values in validation set using Zou-GB/SA score was smaller than that using Grid score, suggesting that the model based on Zou-GB/SA score provides a more effective method for predicting potencies of Cdc7 inhibitors.
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http://dx.doi.org/10.1016/j.ejps.2013.07.013DOI Listing
November 2013

Synthesis, characterization and biodistribution of new fatty acids conjugates bearing N,N,N-donors incorporated [99mTc/Re(CO)3]+.

Dalton Trans 2013 Feb;42(8):2894-901

Key Laboratory of Radiopharmaceuticals of Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, China.

[(99m)Tc(CO)(3)](+)-6-[N-(2-dipicolyl)amino]hexanoic acid (1a) and [(99m)Tc(CO)(3)](+)-11-[N-(2-dipicolyl)amino]undecanoic acid (1b) were prepared by incorporating [(99m)Tc-(CO)(3)](+) into 6-[N-(2-dipicolyl)amino]hexanoic acid and 11-[N-(2-dipicolyl)amino]undecanoic acid, respectively. The overall radiochemical yield of 1a and 1b was from 79.7% to 91.3% and radiochemical purity after HPLC purification was more than 94%. The resulting complexes were found to be chemically stable when incubated in SD rat serum for 3 h at 37 °C. Tissue distribution studies in normal mice showed that high initial uptake of Tc-99m complexes were observed, followed by slow clearance from the heart. The maximum heart-to-blood ratio of 1a was 1.46 at 60 min, but 1b showed a poor heart-to-blood ratio. By estimating the tissue distribution and the computing result of the molar volume and the solvation free energy of Tc-99m chelating groups, a small-size and monocationic Tc-99m core is very important to enhance the myocardial accumulation and low liver uptake for the fatty acid tracers.
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http://dx.doi.org/10.1039/c2dt32492jDOI Listing
February 2013

Molecular modeling studies on benzimidazole carboxamide derivatives as PARP-1 inhibitors using 3D-QSAR and docking.

Chem Biol Drug Des 2011 Sep 29;78(3):333-52. Epub 2011 Jul 29.

Key Laboratory of radiopharmaceuticals of Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, China.

Poly(ADP-ribose) polymerases (PARPs) play significant roles in various cellular functions including DNA repair and control of RNA transcription. PARP-1 inhibitors have been demonstrated to potentiate the effect of cytotoxic agents or radiation in a number of animal tumor models. To understand the structure-activity correlation of cyclic amine-containing benzimidazole carboxamide-based PARP-1 inhibitors, we have carried out a combined molecular docking and three-dimensional quantitative structure-activity relationship (3D-QSAR) modeling study. Two types of satisfactory substructure-based 3D-QSAR models were built, including the comparative molecular field analysis (CoMFA) model (r(2) , 0.913; q(2) , 0.743) and comparative molecular similarity indices analysis (CoMSIA) model (r(2) , 0.869; q(2) , 0.734), to predict the biologic activity of new compounds. Docking studies were performed to explore the binding mode between all of the inhibitors and the PARP-1 and produce the bioactive conformation of each compound in the whole data set. The docked conformer-based alignment strategy gave the best 3D-QSAR models, CoMFA model (r(2) , 0.899; q(2) , 0.712) and CoMSIA model (r(2) , 0.889; q(2) , 0.744), respectively. The structural insights obtained from both the 3D-QSAR contour maps and molecular docking help to better interpret the structure-activity relationship. The information obtained from molecular modeling studies helped us to predict the activity of new inhibitors and further design some novel and potent PARP-1 enzyme inhibitors.
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http://dx.doi.org/10.1111/j.1747-0285.2011.01139.xDOI Listing
September 2011

Combined 3D-QSAR modeling and molecular docking study on 1,4-dihydroindeno[1,2-c]pyrazoles as VEGFR-2 kinase inhibitors.

J Mol Graph Model 2010 Aug 24;29(1):54-71. Epub 2010 Apr 24.

Key Laboratory of radiopharmaceuticals of Ministry of Education, College of Chemistry, Beijing Normal University, Beijing, China.

The vascular endothelial growth factor (VEGF) and its receptor tyrosine kinases VEGFR-2 are attractive targets for the development of novel anticancer agents. To understand the structure-activity correlation of 1,4-dihydroindeno[1,2-c]pyrazole-based VEGFR-2 inhibitors, we have carried out a combined molecular docking and three-dimensional quantitative structure-activity relationship (3D-QSAR) modeling study. The study has resulted in two types of satisfactory substructure-based 3D-QSAR models, including the CoMFA model (r(2), 0.931; q(2), 0.600) and CoMSIA model (r(2), 0.928; q(2), 0.569), for predicting the biological activity of new compounds. The detailed microscopic structures of VEGFR-2 binding with inhibitors have been studied by molecular docking. We have also developed docking based 3D-QSAR models (CoMFA with r(2), 0.958; q(2), 0.563; CoMSIA with r(2), 0.965; q(2), 0.567). The contour maps obtained from the 3D-QSAR models in combination with the docked binding structures help to better interpret the structure-activity relationship. All of the structural insights obtained from both the 3D-QSAR contour maps and molecular docking are consistent with the available experimental activity data. The satisfactory results strongly suggest that the developed 3D-QSAR models and the obtained VEGFR-2 inhibitor binding structures are reasonable for the prediction of the activity of new inhibitors and in future drug design.
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http://dx.doi.org/10.1016/j.jmgm.2010.04.004DOI Listing
August 2010

3D-QSAR studies on a series of inhibitors docked into a new homology model of the DNA-PK receptor.

Curr Pharm Des 2009 ;15(32):3796-825

Key Laboratory of Radiopharmaceuticals of Ministry of Education, College of Chemistry, Beijing Normal University, Beijing, 100875, China.

Cancer therapies through ionizing radiation or chemotherapeutic treatment may result in DNA double strand breaks (DSBs) in cell. DNA-PK has emerged as an attractive target for drug discovery efforts toward DSBs repair and in V(D)J recombination. Hence, the search for potent and selective DNA-PK inhibitors has received particular attention and several series of activity inhibitors have been reported. In this article, we gave a report of the DNA-PK activation and the corresponding inhibitors, which belong to different chemical classes. Then homology modeling and molecular dynamics (MD) simulation were used to build the 3D model of DNA-PK receptor based on the X-ray structure of PI3K. All of the ligands were docked into the putative binding site of the 3D model of DNA-PK using the flexible docking method, and the probable interaction model between DNA-PK and the ligands were obtained. Based on the docking conformations and their alignment inside the binding pocket of DNA-PK, 3D QSAR analyses were performed on 259 ligands using CoMFA and CoMSIA methods. Both CoMFA and CoMSIA provide statistically valid models with good correlation and predictive power (CoMFA: q2 = 0.563, r(2) =0.876; CoMSIA: q(2) = 0.503, r(2) =0.870). Our models would offer help to better comprehend the structure-activity relationship existent for this class of compounds and also facilitate the design of new inhibitors with good chemical derivsity.
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http://dx.doi.org/10.2174/138161209789649484DOI Listing
January 2010

Combined 3D-QSAR modeling and molecular docking study on quinoline derivatives as inhibitors of P-selectin.

Chem Biol Drug Des 2009 Dec 20;74(6):596-610. Epub 2009 Oct 20.

Key Laboratory of Radiopharmaceuticals of Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, China.

P-selectin is a promising target for developing novel atherosclerosis drugs. To understand the structure-activity correlation of quinolines-based P-selectin inhibitors, we have carried out a combined molecular docking and three-dimensional quantitative structure-activity relationship (3D-QSAR) modeling study. The study has resulted in two types of satisfactory 3D-QSAR models, including the CoMFA model (r(2), 0.863; q(2), 0.589) and CoMSIA model (r(2), 0.866; q(2), 0.636), to predict the biological activity of new compounds. The detailed microscopic structures of P-selectin binding with inhibitors have been studied by molecular docking. We have also developed docking based 3D-QSAR models (CoMFA with r(2), 0.934; q(2), 0.591; CoMSIA with r(2), 0.896; q(2), 0.573). The contour maps obtained from the 3D-QSAR models in combination with the docked binding structures help to better interpret the structure-activity relationship. All of the structural insights obtained from both the 3D-QSAR contour maps and molecular docking are consistent with the available experimental activity data. The satisfactory results strongly suggest that the developed 3D-QSAR models and the obtained P-selectin-inhibitor binding structures are reasonable for the prediction of the activity of new inhibitors and in future drug design.
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http://dx.doi.org/10.1111/j.1747-0285.2009.00893.xDOI Listing
December 2009
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