王玉强 教授简介

药物研究的第一步是发现有生物活性的化合物，然后是研究这些化合物的作用机理和药理活性。王玉强实验室主要从事治疗肿瘤、细菌和病毒、心脑血管、老年痴呆和糖尿病等疾病药物的设计、化学合成及药理活性和作用机理的研究。

王玉强教授从事DNA-minor groove binding 药物CC-1065衍生物的研究近20年, 他的实验室合成了100多个CC-1065衍生物, 其中的YW-053是目前已知抗癌活性最强的少数化合物之一，其体外抗癌活性比临床应用的抗癌药物阿霉素强一百万倍 (J. Amer. Chem. Soc. 117, 8917, 1995).
王玉强教授及其团队在美国成功开发抗老年痴呆药物memantine, 该药2009年的销售达13亿美元。他首次设计合成了可以释放一氧化氮的memantine衍生物。这类化合物高度靶向性的结合到大脑神经细胞的NMDA受体并在大脑神经细胞内释放一氧化氮。这类化合物既是NMDA受体的拮抗剂，又能通过一氧化氮的释放而抑制自由基的产生以达到保护神经细胞的目的，因而具有双重作用。
王玉强实验室近年开展了对中药有效成份分子结构进行系统的化学修饰的工作。在中药穿心莲、川芎及丹参有效成份的结构修饰方面已卓有成效，发现了比天然产物疗效更高，毒性更低的新化合物。其中具有独特作用机理和良好治疗效果的糖尿病与脑中风两个新药已正式进入临床前研究。
王玉强教授1981年毕业于山东师范大学化学系, 获学士学位；1987年获美国 The University of Texas Health Science Center at Houston and M. D. Anderson Cancer Center博士学位。随后进入美国耶鲁大学 (Yale) 医学院药理系和加拿大阿尔伯特大学 (The University of Alberta) 化学系做博士后研究。九十年代初进入美国加州硅谷的生物医药公司从事药物的研究与开发工作，2005年回国到暨南大学工作, 现任暨南大学教授，药学院院长，新药研究所所长，博士生导师。

代表性论文
1. Wang, Y.; Farquhar, D. Aldophosphamide acetal diacetate and structural analogues: synthesis and cytotoxicity studies. J. Med. Chem. 34, 197, 1991.
2. Wang, Y.; Liu, M. C.; Lin, T. S.; Sartorelli, A. C. Synthesis and biological evaluation of novel antitumor 3- and 5-hydroxy-4-methyl-2-formylpyridine thiosemicarbazones and their iron-chelates. J. Med. Chem. 35, 3667, 1992.
3. Wang, Y.; Lown, J. L. An alternative method for synthesis of the CC-1065 pharmacophore, 1,2,7,7a-tetrahydrocyclopropa[1,2-c]indol-4-one (CI). Heterocycles 36, 1399, 1993.
4. Wang, Y.; Gupta, R.; Huang, L.; Lown, J. W. Synthesis and antitumor activity of CC-1065 functional analogues possessing different electron-withdrawing substituents and leaving groups. J. Med. Chem. 36, 4172, 1993.
5. Wang, Y.; Huang, L.; Wright, S. C.; Larrick, J. W. Synthesis and antitumor activity studies of doxorubicin and DNA-minor groove binding oligopeptide conjugates. Gene 149, 63, 1994.
6. Fregeau, N. L.; Wang, Y.; Pon, R, T.; Wylie, W. A.; Lown, J. W. Characterization of a CPI-Lexitropsin Conjugate: Oligonucleotide covalent complex by 1H NMR and restrained molecular dynamics simulation. J. Amer. Chem. Soc. 117, 8917, 1995.
7. Wang, Y.; Gupta, R.; Huang, L.; Luo, W.; Lown, J. W. Design, synthesis, cytotoxic properties and preliminary DNA sequencing evaluation of CPI-N-methylpyrrole hybrids. Enhancing effect of a trans double bond linker and role of the terminal amide functionality on cytotoxic potency. Anti-Cancer Drug Design 11, 15, 1996.
8. Wright, S. C.; Schellenberger, U.; Wang, H.; Wang, Y.; Kinder, D. H. Chemotherapeutic drug activation of the AP24 protease in apoptosis: Requirement for caspase 3-like proteases. Biochem. Biophys. Res. Commun. 245, 797, 1998.
9. Wang, Y.; Yuan, H.; Ye, W.; Wang, H.; Wright, S. C.; Larrick, J. W. Synthesis and preliminary biological evaluations of CC-1065 analogs: effects of different linkers and terminal amides on biological activity. J. Med. Chem. 43, 1541. 2000.
10. Wang, Y.; Yuan, H.; Wright, S. C.; Wang, H.; Larrick, J. W. Synthesis and preliminary cytotoxicity study of a cephalosporin-CC-1065 analogue. BMC Chemical Biology 1, 4, 2001.
11. Wang, Y.; Yuan, H.; Wright, S. C.; Wang, H.; Larrick, J. W. Synthesis and cytotoxicity of a biotinylated CC-1065 analogue. BMC Chemical Biology 2, 1. 2002.
12. Wang, Y.; Wright, S. C.; Larrick, J. W. Synthesis and cytotoxicity of nitrogen mustard derivatives of distamycin A. Bioorg. Med. Chem. Lett. 13, 461, 2003.
13. Wang, Y.; Ye, W.; Li, L.; Tian, Z.; Jiang, W.; Wang, H.; Wright, S. C.; Larrick, J. W. CC-1065 analogues bearing different DNA-binding subunits: synthesis, antitumor activity and preliminary toxicity study. J. Med. Chem. 46, 634, 2003.
14. Wang, Y.; Yuan, H.; Wang, H.; Wright, S. C.; Larrick, J. W. Synthesis and preliminary cytotoxicity study of glucuronide derivatives of CC-1065 analogues. Bioorg. Med. Chem. 11, 1569, 2003.
15. Wang, X.; Wang, Y.; Zheng, C. Isolation and purification of honokiol and magnolol from Cortex Magnoliae Officinalis by high-speed counter-current chromatography. J. Chromatography A., 1036, 171, 2004.
16. Wang, X.; Wang, Y.; Yuan, J.; Sun, Q.; Liu, J.; Zheng, C. An efficient new method for extraction, separation and purification of psoralen and isopsoralen from Fructus Psoraleae by supercritical fluid extraction and high-speed counter-current chromatography. J. Chromatography A, 1055, 135, 2004.
17. Wang, Y.; Li, L.; Jiang, W.; Larrick, J. W. Synthesis and evaluation of a DHA and 10-hydroxcamptothecin conjugate. Bioorg. Med. Chem. 13, 5592–5599, 2005.
18. Wang, Y.; Li, L.; Jiang, W.; Yang, Z.; Zhang, Z. Synthesis and preliminary antitumor activity evaluation of a DHA and doxorubicin conjugate. Bioorg. Med. Chem. Lett. 16, 2974-2977，2006.
19. Wang, Y.; Li, L.; Tian, Z.; Jiang, W.; Larrick, J. W. Synthesis and antitumor activity of CBI-bearing ester and carbamate prodrugs of CC-1065 analogue. Bioorg. Med. Chem. 14, 7854-7861, 2006.
20. Wang, Y.; Eu, J.; Washburn, M.; Gong, T.; Chen, H. S. V.; Larrick, J. W.; Lipton, S. A.; Stamler, J, S.; Went, G. T.; Porter, S. The Pharmacology of Aminoadamantane nitrates. Curr. Alzheimer Res. 3, 201-204, 2006.
21. Wang, Y., Yang, Z.; Wright, S. C.; Larrick, J. W. Synthesis and preliminary antitumor activity of distamycin nitrogen mustards. Lett. Drug Design and Discov. 4, 37-39, 2007.
22. Suo, X. B.; Zhang, H.; Wang, Y. HPLC determination of andrographolide in rat whole blood: study on the pharmacokinetics of andrographolide incorporated in liposomes and tablets. Biomed Chromatogr. 21, 730-734, 2007.
23. Suo, X. B.; Deng, Y. J.; Zhang, H.; Wang, Y. Degradation kinetics of water-insoluble lauroyl-indapamide in aqueous solutions: prediction of the stabilities of the drug in liposomes. Arch Pharm Res. 30, 876-883, 2007.
24. Wang, Y.; Jiang, J.; Jiang, X.; Cai, S.; Han, H.; Li, L.; Tian, T.; Jiang, W.; Zhang, Z.; Xiao, Y.; Wei Wright, S. C.; Larrick, J. W. Synthesis and antitumor activity evaluations of albumin-binding prodrugs of CC-1065 analogue. Bioorg. Med. Chem. 16, 6552-6559, 2008.
25. Sun, Y.; Jiang, J.; Zhang, Z.; Yu, P.; Wang, L.; Xu, C.; Liu, W.; Wang, Y. Antioxidative and thrombolytic TMP nitrone for treatment of ischemic stroke. Bioorg. Med. Chem. 16, 8868-8874, 2008.
26. Chen, W-M.; Cheng, C.; Li, B-Z.; Ho, T-L.; Cai, Z-S.; Wang, Y.; Sun, P-H. Pyridine-4-thiol and amphoteric analogs: novel protection of aryl bromides in strong alkali. Helvetica Chimica Acta. 91, 2062-2068, 2008.
27. Guo, J-L.; Li, B-Z.; Chen, W-M.; Sun, P-H.; Wang, Y. Synthesis of substituted 1H-pyrrol-2(5H)-ones and 2(5H)-furanones as inhibitors of P. aeruginosa biofilm. Lett. Drug Design and Discov. 6, 107-113, 2009.
28. Jiang, X.; Yu, P.; Jiang, J.; Zhang, Z.; Wang, Z.; Yang, Z.; Tian, Z.; Wright, S. C.; Larrick, J. W.; Wang, Y. Synthesis and evaluation of antibacterial activities of andrographolide analogues. Eur. J. Med. Chem. 44, 2936-2943, 2009.
29. Chen, J-X.; Xue, H-J.; Ye, W-C.; Fang, B-H., Liu, Y-H., Yuan, S-H., Yu, P.; Wang, Y. Activity of andrographolide and its derivatives against influenza virus in vivo and in vitro. Biol. Pharm. Bull. 32, 1385-1391, 2009.
30. Zhang, Z.; Jiang, J.; Pei Yu, Zeng, X.; Wang, Z.; Larrick, J. W.; Wang, Y. Hypoglycemic and beta cell protective andrographolide analogue for diabetes treatment. J. Translational Med. 7:62, 2009.
31. Xu, J.; Huang, S.; Luo, H.; Li, G.; Bao, J.; Cai, S.; Wang, Y. QSAR studies on andrographolide derivatives as α-glucosidase inhibitors. Int. J. Mol. Sci. 11, 880-895, 2010.
32. Wang, Z.; Yu, P.; Zhang, G.; Xu, L.; Wang, D.; Wang, L.; Zeng, X.; Wang, Y. Design, synthesis and antibacterial activity of novel andrographolide derivatives. Bioorg. Med. Chem. 18, 4269-4274, 2010.
33. Xu, J.; Huang, S.; Luo, H.; Li, G.; Bao, J.; Cai, S.; Wang, Y. QSAR studies on andrographolide derivatives as α-glucosidase inhibitors. Int. J. Mol. Sci. 11, 880-895, 2010.
34. Wang, Z.; Yu, P.; Zhang, G.; Xu, L.; Wang, D.; Wang, L.; Zeng, X.; Wang, Y. Design, synthesis and antibacterial activity of novel andrographolide derivatives. Bioorg. Med. Chem. 18, 4269-4274, 2010.
35. Sun, H.; Xu, L.; Yu, P.; Jiang, J.; Zhang, G.; Wang, Y. Synthesis and preliminary evaluation of neuroprotection of celastrol analogues in PC12 cells. Bioorg. Med. Chem. Lett. 20, 3844-3847, 2010.
36. Zhang, Z.; Li, S.; Jiang, J.; Yu, P.; Liang, J.; Wang, Y. Preventive effects of Flos puerariae lobatae water extract and its active ingredient puerarin in acute and chronic alcohol treated rat and mice model. Chinese Med. 2010 (in press).

部分专利申请
1. Farquhar, D., Wang, Y. Aldophosphamides for treatment of leukemia, US 4,841,085, 1989.
2. Farquhar, D., Wang, Y. Novel antitumor aldophosphamide analogues, US 5,091,552,1992.
3. Farquhar, D., Wang, Y. Novel antitumor aldophosphamide glycoside and dideoxyuridine derivatives, US 5,187,266, 1993.
4. Lown, J. W., Wang, Y., Wei, L. Cyclopropylpyrroloindole-Oligopeptide Anticancer Agents, US 5,502,068, 1996.
5. Wang, Y. Wright, S. C., Larrick, J. W. DNA-binding indole derivatives, their prodrugs and immunoconjugates, US 5,843,937, 1998, 中国专利 ZL97194862.3, 2004.
6. Wang, Y.,Ye, W., Larrick, J. W, Stamler, J. S., Lipton, S. A. Aminoadamantane derivatives as therapeutic agents, US 6,444,702, 2002.
7. Wang, Y.,Ye, W., Larrick, J. W, Stamler, J. S., Lipton, S. A. Aminoadamantane derivatives as therapeutic agents, US 6,620,845, 2003.
8. Wang, Y., Larrick, J. W. Antioxidant nitroxides and nitrones as therapeutic agents. US 6,717,012, 2004.
9. Wang, Y. Novel anticancer conjugates of camptothecin and unsaturated fatty acids. US 6,759416, 2004.
10. Wang, Y., Larrick, J. W. Antioxidant nitroxides and nitrones as therapeutic agents. US 6,852,889, 2005.
11. Wang, Y., Ye, W., Larrick, J. W., Stamler, J. S., Lipton, S. A. Aminoadamantane derivatives as therapeutic agents, US 7,326,730, 2008.
12. Wang, Y., Ye, W., Larrick, J. W., Stamler, J. S., Lipton, S. A. Aminoadamantane derivatives as therapeutic agents, US 7,326,730, 2008.
13. 王玉强, 江晓间, 蒋杰, 张在军, 杨兆琪. 穿心莲内酯衍生物及其在制药中的应用. 发明专利：ZL 200710029644.3, Aug. 2007. PCT国际专利：Andrographolide derivatives and use thereof in manufacture of medicaments. PCT国际申请号：PCT/CN2008/071919. Aug. 2008. 美国专利：USPTO: 12/672,476. Feb. 5, 2010. 欧洲专利：08783912.2, Feb.8, 2010. 日本专利：51000269010, Feb. 8, 2010.
14. 王玉强, 蒋杰, 于沛, 孙业伟, 王林达, 张在军. 一种硝酮类化合物及其制备方法和在制药中的应用. 发明专利申请号200810027706.1, 2008年4月. PCT国际专利：Nitrone compounds, process of preparation thereof, and use thereof in medicament manufacture. PCT国际申请号：PCT/CN2009/071312, 2009年4月.
15. 于沛, 王玉强, 蒋杰, 夏龙飞, 赵景, 张在军. 双酯化喜树碱衍生物及其制备方法和应用. 发明专利申请号200810198272.1 , 2009年6月.
16. 王玉强, 于沛, 蒋杰, 单璐琛, 张高小, 张在军, 陈永红. 丹参素衍生物及其制备方法和应用. 发明专利申请号201010142939.3, 2010年4月.
17. 王玉强, 孙红莉, 徐立朋, 于沛, 张高小, 蒋杰, 单璐琛. 一种雷公藤红素衍生物及其用途. 发明专利申请号20101046812.9, 2010年4月.
18. 王玉强, 于沛, 王中利, 曾祥萍, 徐立朋. 穿心莲内酯衍生物的合成及其在制备药物中的应用. 发明专利申请号201010147341.3, 2010年4月.

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