简单介绍

  博士,教授,药物化学、有机化学博士生导师。1994及1997年分别获武汉大学学士、硕士学位;2000年7月获中山大学生物有机化学专业博士学位。分别于2001.1-2002.1及2002.8-2003.8年在香港科技大学生物技术研究所进行访问研究;2003年底入职中山大学药学院工作至今。先后主持国家自然科学基金、国家高新技术计划863项目、教育部重点科技项目、广东省自然科学基金以及中山大学百人计划引进人才“行动计划”基金等多项研究课题。发表SCI论文80多篇,申请或授权国内外发明专利多项。J Med Chem等多个国际知名学术期刊审稿人,国家、省基金评审专家,省药学会成员。

研究方向

    药学多学科融合基础上的药物设计与发现:

    1) 活性多肽、类天然产物库的构建;

    2) 肿瘤、神经退行性疾病恶性事件中关键蛋白的降解与折叠行为调控及药理意义;

    3) 重大疾病相关信号网络关键因子的探针设计与药物发现

    科研项目

     

    1. 基于蛋白N端捕获的活性环肽设计及其抗AD作用与分子机制研究(21672266), 国家自然科学基金,2017.1-2020.12

    2. 靶向19SRP去泛素化酶的新机制蛋白酶体抑制剂的发现与抗肿瘤研究(81473083), 国家自然科学基金,2015.1-2018.12

    3. 靶向NF-kappaB/p53交叉通路网络的新型PAC类抗肿瘤活性分子的设计发现与机制研究(81172931),国家自然科学基金,2012.1-2015.12

    4. 抑制NF-κB激活通路的新型PACs类先导物的发现、作用机制及抗肿瘤研究(30973619),国家自然科学基金,2010.1-2012.12

    5. 神经退行性疾病信号转导及新靶标研究(批准号:9351008901000003),广东省自然科学基金研究团队项目,2010.1-2012.12(核心成员)

    6. 多靶标内环境激活式抗耐药肿瘤先导分子的设计(2008AA02Z304);国家高新技术863项目,2008.1-2010.12

    7. 基质细胞衍生因子衍生多肽库的构建及其抗肿瘤转移作用研究(5001773),广东省自然科学基金2005.1-2007.12

    8. 抑制CXCR4的重组趋化因子衍生肽库的构建及其生理意义(105133),国家教育部重点科技项目2005.1-2007.12

    9. 中山大学百人计划引进人才“行动计划”基金,2003

     

    论著专利

    1. Gesi Wen1, Daoyuan Chen1, Wenjing Qin, Binhua Zhou, Youqiao Wang, Ziyi Liu, Jun Du, Qiang Zhou, Junmin Quan, Xianzhang Bu*, Stabilizing of Amyloid-β Peptide by the N-terminus Capture is Capable of Preventing and Eliminating Amyloid-β Oligomers. Chem. Commun., 2017, 53, 7673—7676

    2. Xin Yue1, Yinglin Zuo1, Hongpeng Ke, Jiaming Luo, lanlan Lou, Wenjing Qin, Youqiao Wang, Ziyi Liu, Daoyuan Chen, Haixia Sun, Weichao Zheng, Cuige Zhu, Ruimin Wang, Gesi Wen, Jun Du, Binhua Zhou*, Xianzhang Bu*, Identification of 4-arylidende curcumin analogues as novel proteasome inhibitors for potential anticancer agents targeting 19S regulatory particle associated deubiquitinase. Biochem Pharmacol 2017, 137, 29-50.

    3. Gesi Wen, Wenjing Qin, Daoyuan Chen, Youqiao Wang, Xin Yue, Ziyi Liu, Yingnan Cao, Jun Du, Binhua Zhou*, and Xianzhang Bu*, Stabilizing the monomeric amyloid-β peptide by Tyrocidine A prevents and reverses the amyloideogenesis without the accumulation of oligomers Chem. Commun., 2017, 53, 3886-3889.

    4. Baoxia Liang, Ziyi Liu, Yingnan Cao, Cuige Zhu, Yinglin Zuo, Lei Huang, Gesi Wen, Nana Shang, Yu Chen, Xin Yue, Jun Du, Baojian Li, Binhua Zhou*, Xianzhang Bua*, MC37, a new mono-carbonyl curcumin analog, induces G2/M cell cycle arrest and mitochondria-mediated apoptosis in human colorectal cancer cells. European Journal of Pharmacology 2016, 796,139-148.

    5. Jianyong Zhu, Ruimin Wang, Lanlan Lou, Wei Li, Guihua Tang, Xianzhang Bu*, and Sheng Yin*, Jatrophane Diterpenoids as Modulators of P-Glycoprotein-Dependent Multidrug Resistance (MDR): Advances of Structure–Activity Relationships and Discovery of Promising MDR Reversal Agents, J. Med. Chem., 2016, 59(13):6353-6369

    6. Baoxia Liang, Weiyan Shao, Cuige Zhu, Gesi Wen, Xin Yue, Ruimin Wang, Junmin Quan, Jun Du, and Xianzhang Bu*, Mitochondria-Targeted Approach: Remarkably Enhanced Cellular Bioactivities of TPP2a as Selective Inhibitor and Probe toward TrxR, ACS Chem. Biol., 2016, 11 (2), 425–434

    7. Zhang-Hua Sun, Yu Chen, Yan-Qiong Guo, Jie Qiu, Cui-Ge Zhu, Jing Jin, Gui-Hua Tang, Xian-Zhang Bu*, Sheng Yin*, Isolation and cytotoxicity evaluation of taxanes from the barks of Taxus wallichiana var. mairei, Bioorganic & Medicinal Chemistry Letters, 2015, 25, 1240–1243

    8. Cuige Zhu, Yinglin Zuo, Baoxia Liang, Hong Yue, Xin Yue, Gesi Wen, Ruimin Wang, Junmin Quan, Jun Du and Xianzhang Bu* Distinct tubulin dynamics in cancer cells explored using a highly tubulin-specific fluorescent probeChem. Commun., 2015,  51, 13400-13403.

    9. Cuige Zhu , Yinglin Zuo , Ruimin Wang , Baoxia Liang , Xin Yue , Gesi Wen , Nana Shang , Lei Huang , Yu Chen , Jun Du , and Xianzhang Bu * Discovery of Potent Cytotoxic Ortho-Aryl Chalcones as New Scaffold Targeting Tubulin and Mitosis with Affinity-Based FluorescenceJ. Med. Chem., 2014, 57 (15), 6364–6382.

    10. L. Huang, Y. Chen, B. Liang, B. XING, G. Wen, S. Wang, X. Yue, C. Zhu, J. Du and X. Bu, Furanyl Acryl Conjugated Coumarin as Efficient Inhibitor and Highly Selective Off-On Fluorescent Probe for Covalent Labelling of Thioredoxin Reductase Chem. Commun., 2014,  50, 6987--6990.

    11. Nana Shanga, Yongxian Shao, Yinghong Cai, Matthew Guan, Manna Huang, Wenjun Cui, Lin He, Yan-Jun Yu, Lei Huang, Zhe Li, Xianzhang Bu*, Hengming Ke*, Hai-Bin Luo*, Discovery of 3-(4-hydroxybenzyl)-1-(thiophen-2-yl)chromeno[2,3-c]pyrrol-9(2H)- one as a phosphodiesterase-5 inhibitor and its complex crystal structure, Biochemical Pharmacology 2014, 89, 86–98 .

    12. H. Liu, Y. Liu, F. Zhang, H. Wang, G. Zhang, B. Zhou, Y. Zuo, S. Cai, X. Bu* and J. Du*, Identification of potential pathways involved in induction of cell cycle arrest and apoptosis by a new 4-arylidene Curcumin analogue T63 in lung cancer cells: a comparative proteomic analysis Mol. BioSyst., 2014, 10, 1320—1331.

    13. Binhua Zhou, Yinglin Zuo, Baojian Li, Hao Wang, Hao Liu, Xianfeng Wang, Xu Qiu, Yun Hu, Shijun Wen, Jun Du, Xianzhang Bu*, Deubiquitinase Inhibition of 19S Regulatory Particles by 4-Arylidene Curcumin Analogue AC17 Causes NF-κB Inhibition and p53 Reactivation in Human Lung Cancer Cells, Molecular Cancer Therapeutics, 2013, 12(8), 1381–1392.

    14. Yun Hu, Yaqi Yang, Yanjun Yu, Gesi Wen, Nana Shang, Wei Zhuang, Dihan Lu, Binhua Zhou, Xin Yue, Baoxia Liang, Jun Du, Feng Li, Xian-Zhang Bu*, Synthesis and Identification of New Flavonoids Targeting Liver X Receptor β Involved Pathway as Potential Facilitators of Aβ Clearance with Reduced Lipid Accumulation. Journal of Medicinal Chemistry, 2013, 56, 6033−6053.

    15. Binhua Zhou, Jianing Huang, Yinglin Zuo, Baojian Li, Qiang Guo, Baicheng Cui, Weiyan Shao, Jun Du, Xianzhang Bu*, 2a, a novel curcumin analogue, sensitizes cisplatin-resistant A549 cells to cisplatin by inhibiting thioredoxin reductase concomitant oxidative stress damage, European Journal of Pharmacology, 2013, 707, 130‐139.

    16. Hao Liu, BinHua Zhou, Xu Qiu, HongSheng Wang, Fan Zhang, Rui Fang, XianFeng Wang, ShaoHui Cai, Jun Du*, XianZhang Bu*T63, a new 4-arylidene curcumin analogue,induces cell cycle arrest and apoptosis through activation of the reactive oxygen species–FOXO3a pathway in lung cancer cellsFree Radical Biology and Medicine, 2012, 53, 2204–2217.

    17. Yinglin Zuo, Jianing Huang, Binhua Zhou, Shuni Wang, Weiyan Shao, Cuige Zhu, Li Lin, Gesi Wen, Hongyang Wang, Jun Du, Xianzhang Bu*  Synthesis, cytotoxicity of new 4-arylidene curcumin analogues and their multi-functions in inhibition of both NF-kB and Akt signaling, Europe Journal of Medicinal Chemistry, 2012, 55, 346-357.

    18. Yinglin Zuo, Yi Yu, Shuni Wang, Weiyan Shao, Binhua Zhou, Li Lin, Zhuoyu Luo, Ruogu Huang, Jun Du, Xianzhang Bu* Synthesis and cytotoxicity evaluation of biaryl-based chalcones and their potential in TNFa-induced nuclear factor-kB activation inhibition Europe Journal of Medicinal Chemistry, 2012, 50, 393-404.

    19. Yanjun Yu, Yun Hu, Weiyan Shao, Jianing Huang, Yinglin Zuo, Yingpeng Huo, Linkun An, Jun Du, and Xianzhang Bu* Synthesis of Multi-Functionalized Chromeno[2,3-c]pyrrol-9(2H)-ones: Investigation and Application of Baker–Venkataraman Rearrangement Involved Reactions Catalyzed by 4-(Dimethylamino)pyridine, Europe Journal of Organic Chemistry, 2011, 4551–4563 (IF:3.344)

    20. X Qiu, YH Du, B Lou, YL Zuo, WY Shao, YP Huo, JL Huang, YJ Yu, BH Zhou,J Du HA Fu* and  XZ Bu*, Synthesis and Identification of New 4-Arylidene Curcumin Analogues as Potential Anticancer Agents Targeting Nuclear Factor-kB Signaling Pathway. J Med Chem, 2010. 53 (23), 8260–8273.

    21. MG Yuan, MX Luo, Y Zhang, X Qiu, J Gui, Y Cao, X. Bu*, YL Ren* and XP Hu, Identification of curcumin derivatives as human glyoxalase I inhibitors: A combination of biological evaluation, molecular docking, 3D-QSAR and molecular dynamics simulation studies Bioorg & Med Chem  2011193):1189-1196

    22. Z Xiao, LM Lin, ZH Liu, FT Jia, WY Shao, MJ Wang,L Liu, SL Li, F Li* and Bu, X.*, Potential Therapeutic Effects of Curcumin: Relationship to Microtubule- associated Proteins 2 in Abeta1-42 Insult. Brain Res  2010, 1361, 115-123

    23. Y.Huo, X Qiu, WY Shao, JN Huang, YJ Yu, YL Zuo, LK An, J Du and Bu, X.* , New fluorescent trans-dihydrofluoren-3-ones from aldol-Robinson annulation- regioselective addition involved one-pot reaction. Org Biomol Chem 2010. 8, 5048–5052

    24. Shen, Y.D., Tian Y.X, Bu, X. Z.* and L.Q. Gu, Natural tanshinone-like heterocyclic-fused ortho-quinones from regioselective Diels-Alder reaction: Synthesis and cytotoxicity evaluation. Eur J Med Chem 2009, 44, 3915-3921.

    25. Qiu, X.; Liu, Z.; Shao, W.Y.; Liu,X.; Jing, D.P.; Lu, Y.J.; An, L.K.; Huang, S.L.; Bu, X.Z.*; Huang, Z. S.; Gu, L.Q., Synthesis and evaluation of curcumin analogues as potential thioredoxin reductase inhibitors. Bioorgan Med Chem 2008, 16, 8035-8041.

    26. Shao, W.Y.; Cao, Y.N.; Yu, Z.W.; Pan, W.J.; Qiu, X.; Bu, X.Z.*; An, L. K.; Huang, Z. S.; Gu, L.Q.*; Chan, A. S. C. Facile preparation of new unsymmetrical curcumin derivatives by solid-phase synthesis strategy. Tetrahedron Lett 2006, 47, 4085-4089.

    27. Pei, L. X.; Li, Y.M.; Bu, X.Z.*; Gu, L.Q.; Chan, A. S. C. One-pot synthesis of 5,6-dihydroxylated benzo[b]furan derivatives. Tetrahedron Lett 2006, 47, 2615-2618.

    28. Shen, Y.D.; Wu, H.Q.; Zhang, S.L.; Bu, X.Z.*; An, L.K.; Huang, Z.S.; Liu, P.Q.; Gu, L.Q.; Li, Y.M. and Chan, A.S.C. Novel synthesis of o-naphthothiophenequinone derivatives via regioselective Diels-Alder reaction. Tetrahedron 2005, 61, 9097-9101.

    29. Pei, L.X.; Huang, S.L.; Shen, Y.D.; An, L.Q.; Huang, Z.S.; Li, Y.M.; Gu, L.Q.*; Bu, X.Z.* and Chan, A.S.C. Synthesis of novel dihydrofuro[b]-pyridinone derivatives: oxidation coupling of 3-hydroxy-4(1H)-pyridinone with beta-dicarbonyl compounds. Tetrahedron Lett 2005, 46, 5085-5088.

    30. Bu, X.Z.; Wu, X.M.; Ng, N.L.J.; Mak, C.K.; Qin, C.G.; Guo, Z.H. Synthesis of gramicidin S and its analogues via an on-resin macrolactamization assisted by a predisposed conformation of the linear precursors. J Org Chem 2004, 69, 2681-2685.

    31. Bu, X.Z.; Xie, G.Y.; Law, C.W.; Guo, Z.H. An improved deblocking agent for direct Fmoc solid-phase synthesis of peptide thioesters. Tetrahedron Lett 2002, 43, 2419-2422.

    32. Bu, X.Z.; Wu, X.M.; Xie, G.Y.; Guo, Z.H. Synthesis of tyrocidine A and its analogues by spontaneous cyclization in aqueous solution. Org Lett 2002, 4, 2893-2895.

    33. Bu, X.Z.; Huang, Z.S.; Zhang, M.; Ma, L.; Xiao, G.W.; Gu, L.Q. Synthesis of new 1,1-dimethyl-1,2,3,4-tetrahydrophenanthrene derivatives. Tetrahedron Lett 2001, 42, 5737-5740.

    34. 卜宪章,陈道远,温格思,一类环十肽分子及其应用,申请号:201710104115.9;申请日期:2017.02.24

    35. 卜宪章,朱翠革,岳欣,左应林,陈雨,温格思,邻苯基查尔酮类化合物及其制备方法和应用,申请号:PCT/CN2015/070651,申请日期:2015.01.14;国际专利PCT申请

    36. 卜宪章,朱翠革,左应林,杜军,温格思,岳欣,陈雨,一种邻苯基查尔酮类化合物在荧光探针中的应用,申请号:201410353793.5;申请日期:2014.07.23

    37. 卜宪章,朱翠革,岳欣,左应林,陈雨,温格思,邻苯基查尔酮类化合物及其制备方法和应用,申请号:201410032845.9;申请日期:2014.01.23,授权公告日,2016.06.08

    38. 卜宪章,吴海强,黄磊,一种硫氧还蛋白还原酶荧光探针及其制备方法和用途,申请号:201410137070.1;申请日期:2014.04.08

    39. 卜宪章,罗海彬,商娜娜,于艳君,杜军,李哲,蔡颖红,邵咏贤,何琳,一种取代吡咯色原酮类化合物在制备治疗5型磷酸二酯酶相关疾病的药物中的应用,申请号:201310017288.9;申请日期:2013.01.17, 授权公告日:2015.8.26

    40. 卜宪章,刘培庆,于艳君,汪煜华,胡云,邵伟艳,杜军,羟基取代的黄酮类化合物及其制备方法和应用。中华人民共和国知识产权局。申请号:201110269084.5.申请日期:2011913

    41. 卜宪章,胡云,于艳君,杜军,邵伟艳,商娜娜,庄玮,陆迪涵,刘巍,陈艺贞,温格思,氨基取代的黄酮类化合物及其制备方法和应用。中华人民共和国知识产权局。申请号:201110269753.9 申请日期:2011913日,授权公告日:2014.6.11

    42. 卜宪章 左应林 杜军 温格斯 周斌华 商娜娜,芳基取代查尔酮类化合物及其制备方法和应用 中国专利申请号:201110217094.4 授权公告日:20131225

    43. 卜宪章 于艳君 邵伟艳 胡云 黄壮裕 左应林,一种多多取代色原酮并吡咯环类衍生物及其合成方法和应用,中国发明专利,专利号:ZL200910214553.6,申请日:2009.12.31 授权公告日:2012.6.27

    44. 卜宪章,仇旭,霍应鹏,于艳君,金达平,古练权,具有抗肿瘤作用的多芳乙烯取代beta-二酮类化合物,中国发明专利,申请号:200810220580.X, 申请日:2008.12.30,授权公告号 CN101700995B,授权公告日:2013.06.05

    45. 卜宪章,邵伟艳,古练权,曹颖男,于志文,一种合成多肽及其应用,中国发明专利,专利号:ZL 200410077777.4, 授权公告日:2007.2.21