徐文方
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- 姓名:徐文方
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学术头衔:
博士生导师
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学科领域:
细胞生物学
- 研究兴趣:
徐文方,男,1952年10月生,山东大学药学院副院长、校聘关键岗教授,博士研究生导师,九届山东省政协常委。主要学术兼职有:中国药学会药物化学专业委员会委员, 中国抗癌协会抗癌药物专业委员会委员,国家SDA新药评审专家委员会成员,国家基本药物遴选委员会成员,全国医药教材评审委员会委员,教育部教学指导委员会制药工程专业副主任委员,山东省药学会常务理事兼药物化学与抗生素专业委员会主任委员,山东大学学报(医学板)、中国药物化学杂志、肿瘤防治等杂志编委,Bioorg Med Chem杂志特邀审稿人,全国医药规划教材《药物化学》主编。近五年来,主持承担了国家科技部国际合作重点项目、国家自然科学基金、教育部博士点基金、山东省自然科学基金等科研项目及多项与企业横向联合研究课题。在国内外SCI及核心期刊发表论文80多篇,出版著作或主编教材5部。作为第一获奖人,先后获得省部级科技进步奖五项,国家新药证书五项。指导着博士后、博士、硕士研究生20多名。1999年荣获济南市“为四化建功立业劳动奖章”,享受国务院政府特殊津贴。2004年被授予全国师德先进个人、山东省优秀教师、山东大学十大教学名师荣誉称号。
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成果数
11
徐文方, Wenfang Xu, Zhen Zhang
Drugs of the Future 2001,26(10): 935-938,-0001,():
-1年11月30日
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【期刊论文】Investigation of lectin-modified insulin liposomes as carriers for oral administration
徐文方, Na Zhang a, Qi N. Ping b, Gui H. Huanga, Wen F. Xua, *
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-1年11月30日
The aim of this study was to design and characterize lectin-modified liposomes containing insulin and to evaluate the potential of these modified colloidal carriers for oral administration of peptide and protein drugs. Wheat germ agglutinin (WGA), tomato lectin (TL), or Ulex europaeus agglutinin 1 (UEA1) were conjugated by coupling their amino groups to carbodiimide-activated carboxylic groups of N-glutaryl-phosphatidylethanolamine (N-glut-PE). Insulin dispersions were prepared by the reverse-phase evaporation technique and modified with the lectin-N-glut-PE conjugates. Lectin-modified liposomes were characterized according to particles size, zeta potential and entrapment efficiency. The hypoglycemic effect of the lectin-modified pharmacological bioavailability of insulin liposomes modified with WGA, TL and UEA1 were 21.40, 16.71 and 8.38% in diabetic mice as comparison with abdominal cavity injection of insulin, respectively. After oral administration of the insulin liposomes modified with WGA, TL and UEA1 to rats, the relative pharmacological bioavailabilities were 8.47, 7.29 and 4.85%, the relative bioavailability were 9.12, 7.89 and 5.37% in comparison with subcutaneous injection of insulin, respectively. In the two cases, no remarkable hypoglycemic effects were observed with the conventional insulin liposomes. These results confirmed that lectin-modified liposomes promote the oral absorption of insulin due to the specific-site combination on GI cell membrane.
Wheat germ agglutinin, Tomato lectin, Ulex europaeus agglutinin 1, Insulin, Liposomes, Oral administration
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【期刊论文】The preparation of novel L-iso-glutamine derivatives as potential antitumor agents†
徐文方, Jun-li Wang and Wen-fang Xu*
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-1年11月30日
A series of novel L-iso-glutamine derivatives were prepared by condensing of compound 4 with various amino acid methyl esters. These compounds have not been reported in literature, and their chemical structures were confirmed by ESI-MS, IR and NMR.
preparation,, L-iso-glutamine,, derivatives
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徐文方, LI Xun XU Wen-Fang
,-0001,():
-1年11月30日
The crystal structure of (4S)-5-(2-methoxy-2-oxoethylamino)-5-oxo-4-(3,4,5-trimethoxybenzamido) pentanoic acid 5 (C18H24N2O9, Mr=412.39) has been determined by single-crystal X-ray diffraction analysis. The crystal belongs to monoclinic, space group P2(1)/c with a=27.665(9), b=5.1444(16), c=13.907(4) Å, β=98.401(5)º, V=1958.0(11) Å3, Z=4, Dc=1.399 g/cm3, μ=0.113mm-1, F(000)=872, R=0.0606 and wR=0.1405 (I>2σ(I)). The results confirmed that 5 could be assigned to the tautomeric form. The intermolecular hydrogen bonds between O(5)-H(5)…O(7), N(2)-H(2)…O(6) and N(1)-H(1)…O(4) have been observed.
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【期刊论文】Progress in the Development of Aminopeptidase N (APN/CD13) Inhibitors
徐文方, Wenfang Xu* and Qianbin Li
Curr. Med. Chem. - Anti-Cancer Agents, 2005, 5, 000-000,-0001,():
-1年11月30日
Aminopeptidase N (APN; CD13) is a member of zinc-containing ectoenzymes family involved in the degradation of neutral or basic amino acids (Ala>Phe>Leu>Gly) from N-terminal of bioactive peptides and amide or arylamide derivatives of amino acids. The expression of APN being up regulated has been implicated in the pathogenesi of a variety of diseases such as cancer, leukemia, diabetic nephropathy, and rheumatoid arthritis. Thus, APN inhibitors (APNIs) are expected to be useful for the treatment of these disorders. This article reviews briefly the structure characteristic and possible function of APN. The proposed biomolecular structures and mechanism of action used in the design of APNIs are thoroughly covered. Major emphasis is on recently published potent, small molecular weight APNIs and their essential structure activity relationship (SAR). Finally, available clinical results of compounds in development are summarized in this review.
Aminopeptidase N,, inhibitors,, mechanisms.,
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【期刊论文】Novel Anticancer Targets and Drug Discovery in Post Genomic Age
徐文方, Qianbin Li and Wenfang Xu*
Curr. Med. Chem. - Anti-Cancer Agents, 2005, 5, 53-63,-0001,():
-1年11月30日
Cancer is a serious disease with a complex pathogenesis, which threats human life greatly. Currently, great efforts have been put to the identification of novel anticancer targets and the discovery of anticancer drugs following the progress of chemogenomics, which will be reviewed briefly in this article. Furthermore, during the past 5 years, the global effort of sequencing human genome has provided us with an enormous number of potential targets associated with cancer therapy. As a result, the New Drug Discovery (NDD) is undergoing a transition "from gene to drug". Accordingly, the targets for anticancer drugs studies now are focused on some biological macromolecular targets associated with cancer and several interactive mechanisms involved in the growth and metastasis of cancer cells as well as tumorangiogenesis, such as Matrix Metalloproteinases (MMPs), Aminopeptidase N (APN), Tyrosine Kinase (TK), Farnesyltransferase (FTase) and cell Signal Transduction Pathway and so forth. Among these targets the MMP-2, -9 and APN are the most extensively studied enzymes in our laboratory. The peptidomimetics Matrix Metalloproteinase Inhibitors (MMPIs) and APN inhibitors (APNIs) with the molecular scaffold of pyrrolidine, 3-amino-2-hydroxy-4-phenyl butyric acid (AHPA) and glutamylide, which have been designed and synthesized in our laboratory, will be described in the review, among which the pyrrolidine scaffold is patented with the IC50 ranging from 1nM to 300nM against MMP-2, and MMP-9.
Novel anticancer targets,, matrix metalloproteinases,, aminopeptidase N,, tyrosine kinase,, farnesyltransferase,, inhibitor/, manipulators.,
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徐文方, Xin Yong LIU*, Wen Fang XU, Jing De WU
Chinese Chemical Letters Vol. 14, No. 8, pp 790-793, 2003,-0001,():
-1年11月30日
A series of novel 3-alkylthio-4-arylideneamino-5-(2-furyl)-1, 2, 4-triazole derivatives were synthesized. Their chemical structures were confirmed with elemental analysis and spectral data. Endothelin(ET) receptor competitive binding assay showed that some compounds exhibited high selective as potent ET-1 receptor antagonist.
1,, 2,, 4-Triazole derivatives,, ET antagonist.,
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徐文方, Xinyong Liu, a, * Rui Zhang, a Wenfang Xu, a Chaowu Li, b Quanqin Zhao c and Xingpo Wangc
Bioorganic & Medicinal Chemistry Letters 13 (2003) 2123-2126,-0001,():
-1年11月30日
A series of novel 2-acyloxymethyl-3,5,6-trimethylpyrazine derivatives was designed and synthesized. Most compounds were found to be 1.5-4.5-fold higher potency than tetramethylpyrazine (TMP) in stimulating the proliferation of normal vascular endothelial cells and in protecting against hyperoxic acute injury. The most active one is the 2-nicotinoyl ester 5a exhibiting the maximum proliferation rate (Pmax) of 88.57% at the concentration of 0.1 mmol L1. Structure-activity relationships of these compounds were discussed.
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徐文方, Ya-Lin Li and Wen-Fang Xu*
Bioorganic & Medicinal Chemistry 12 (2004) 5171-5180,-0001,():
-1年11月30日
The synthesis and biological evaluation of caffonyl pyrrolidine derivatives as MMPs inhibitors are reported in this paper. Inhibiting activities of synthesized compounds on gelatinase (MMP-2 and -9) were tested by using succinylated gelatin as substrate. Structure-activity relationship results from these tested compounds demonstrated that longer and more flexible side chain linked to the pyrrolidine ring at C4 produced higher activity at gelatinase. Furthermore, aromatic heterocycle and sulfamide in the same position could enhance the activities. Compounds with free phenol hydroxyl group showed higher activity compared to methylated derivatives (or counterparts), which confirms the importance of phenol hydroxyl functionality in the interaction with gelatinase. The anti-metastasis model of mice bearing H22 tumor cell was used to evaluate their in vivo inhibiting activities. All tested compounds were orally administered at a dose of 50 or 100mg/kg, 6days/week for two weeks. The test results demonstrated that most of these inhibitors showed significant anti-cancer activities (inhibitory rate > 35%) and were devoid of toxic effects. Compound 29 showed the highest inhibitory rate at 69.25%, indicating that it might be a promising lead compound.
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【期刊论文】Structure confirmation of L-iso-glutamine derivatives
徐文方, Xun LI, Jun-Li WANG and Wen-Fang XU*
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-1年11月30日
L-iso-glutamine derivatives as an APNIs was prepared by the condensation reaction of N-(3,4,5-trimethoxybenzoyl)-glutamic acid anhydride with L-amino acid methyl ester hydrochloride. The structure was confirmed by the methods of IR, 1H NMR, MS, elemental analysis, HMBC Spectrum and X-ray single crystal diffraction.
APN,, L-iso-glutamine derivatives,, APN inhibitors,, Structure confirmation
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