人物經歷
1981年畢業於山東師範大學化學系,獲學士學位;
1987年獲美國University of Texas Health Science Center at Houston and M. D. Anderson Cancer Center博士學位。 隨後進入美國耶魯大學 (Yale) 醫學院和加拿大阿爾伯特大學 (University of Alberta) 做博士後研究。
九十年代初進入美國加州矽谷的生物醫藥公司從事藥物的研究與開發,2005年回國任暨南大學教授,藥學院院長,現任暨南大學新藥研究所所長,博士生導師。
2010年獲廣州經濟技術開發區科技領軍人才稱號。
研究方向
藥物研究的第一步是發現有生物活性的化合物,然後是研究這些化合物的作用機理和藥理活性。王玉強實驗室目前主要從事抗細菌和病毒藥物、治療糖尿病、心血管疾病藥物如心肌缺血、神經退行性疾病如老年痴呆和帕金森等疾病藥物的設計、化學合成、藥理活性與作用機理的研究。
主要貢獻
王玉強實驗室近年開展了對中藥有效成份分子結構進行系統的化學修飾的工作。在中藥穿心蓮、川芎及丹參有效成份的結構修飾方面已卓有成效,發現了比天然產物療效更高,毒性更低的新化合物。其中具有獨特作用機理和良好治療效果的治療缺血性腦中風新藥已完成臨床前研究。
主要論文
1.Farquhar, D.; Wang, Y. Novel antitumor organophosphates. The Cancer Bulletin Vol. 37, No.4. 167, 1985.
2.Beran, M.; Andersson, B. S.; Wang, Y.; McCredie, K. B.; Farquhar, D. The effects of acetalaldophosphamide, a novel stable aldophosphamide analogue, on normal hu-man and leukemic progenitor cells in vitro: Implications for use in bone marrow purg-ing. Cancer Res. 48, 339, 1988.
3.Andersson, B. S.; Wang, Y.; Farquhar, D. Stable in vitro active aldophosphamide acetals for bone marrow purging. Autologous Bone Marrow Transplantation, in pro-ceedings of the fourth international symposium. 1989.
4.Andersson, B. S.; Wang, Y.; McCredie, K. B.; Farquhar, D. Suitability of a new stable acetal analogue of aldoifosphamide for purging leukemic cells from human bon-e marrow. Leukemia 6, 435, 1990.
5. Wang, Y.; Farquhar, D. Aldophosphamide acetal diacetate and structural analogu-es: synthesis and cytotoxicity studies. J. Med. Chem. 34, 197, 1991.
6. Wang, Y.; Liu, M. C.; Lin, T. S.; Sartorelli, A. C. Synthesis and biological evaluat-ion of novel antitumor 3- and 5-hydroxy-4-methyl-2-formylpyridine thiosemicarba-zones and their iron-chelates. J. Med. Chem. 35, 3667, 1992.
7. Wang, Y.; Lown, J. L. An alternative method for synthesis of the CC-1065 pharm-acophore, 1,2,7,7a-tetrahydrocyclopropa[1,2- c]indol-4-one (CI). Heterocycl-es 36, 1399, 1993.
8. Wang, Y.; Gupta, R.; Huang, L.; Lown, J. W. Synthesis and antitumor activity of CC-1065 functional analogues possessing different electron-withdrawing substitue-nts and leaving groups. J. Med. Chem. 36, 4172, 1993.
9. Wang, Y.; Huang, L.; Wright, S. C.; Larrick, J. W. Synthesis and antitumor activ-ity studies of doxorubicin and DNA-minor groove binding oligopeptide conjuga-tes. Gene 149, 63, 1994.
10.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 re-strained molecular dynamics simulation. J. Amer. Chem. Soc. 117, 8917, 1995.
11. Wang, Y.; Gupta, R.; Huang, L.; Luo, W.; Lown, J. W. Design, synthesis, cyto-toxic properties and preliminary DNA sequencing evaluation of CPI- N-methy-lpyrrole 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.
12.Wright, S. C.; Schellenberger, U.; Wang, H.; Wang, Y.; Kinder, D. H. Chemother-apeutic drug activation of the AP24 protease in apoptosis: Requirement for caspase 3-like proteases. Biochem. Biophys. Res. Commun. 245, 797, 1998.
13. Wang, Y.; Yuan, H.; Ye, W.; Wang, H.; Wright, S. C.; Larrick, J. W. Synthesis and pre-liminary biological evaluations of CC-1065 analogs: effects of different link-ers and terminal amides on biological activity. J. Med. Chem. 43, 1541. 2000.
14. Wang, Y.; Yuan, H.; Wright, S. C.; Wang, H.; Larrick, J. W. Synthesis and pre-liminary cytotoxicity study of a cephalosporin-CC-1065 analogue. BMC Chemical Biology 1, 4, 2001.
15. Wang, Y.; Yuan, H.; Wright, S. C.; Wang, H.; Larrick, J. W. Synthesis and cyto-toxicity of a biotinylated CC-1065 analogue. BMC Chemical Biology 2, 1. 2002.
16. 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.
17. 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.
18. Wang, Y.; Yuan, H.; Wang, H.; Wright, S. C.; Larrick, J. W. Synthesis and pre-liminary cytotoxicity study of glucuronide derivatives of CC-1065 analogues. Bioorg. Med. Chem. 11, 1569, 2003.
19.Wang, X.; Wang, Y.; Zheng, C. Isolation and purification of honokiol and magno-lol from Cortex Magnoliae Officinalis by high-speed counter-current chromatogra-phy. J. Chromatography A., 1036, 171, 2004.
20.Wang, X.; Wang, Y.; Yuan, J.; Sun, Q.; Liu, J.; Zheng, C. An efficient new me-thod 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.
21. 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.
22. Wang, Y.; Li, L.; Jiang, W.; Yang, Z.; Zhang, Z. Synthesis and preliminary anti-tumor activity evaluation of a DHA and doxorubicin conjugate. Bioorg. Med. Chem. Lett. 16, 2974–2977, 2006.
23. Wang, Y.; Li, L.; Tian, Z.; Jiang, W.; Larrick, J. W. Synthesis and antitumor act-ivity of CBI-bearing ester and carbamate prodrugs of CC-1065 analogue. Bioorg. Med. Chem. 14, 7854–7861, 2006.
24. 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.
25. Wang, Y., Yang, Z.; Wright, S. C.; Larrick, J. W. Synthesis and preliminary anti-tumor activity of distamycin nitrogen mustards. Lett. Drug Design and Discov. 4, 37–39, 2007.
26.Suo, X. B.; Zhang, H.;Wang, Y. HPLC determination of andrographolide in rat whole blood: study on the pharmacokinetics of andrographolide incorporated in lipo-somes and tablets.
Biomed Chromatogr.21, 730–734,2007.
27.Suo, X. B.; Deng, Y. J.; Zhang, H.; Wang, Y. Degradation kinetics of waterinsol-uble lauroyl-indapamide in aqueous solutions: prediction of the stabilities of the drug in liposomes. Arch Pharm Res. 30, 876–883, 2007.
28. 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 activ-ity eva-luations of albumin-binding prodrugs of CC-1065 analogue. Bioorg. Med. Chem. 16, 6552–6559, 2008.
29.Sun, Y.; Jiang, J.; Zhang, Z.; Yu, P.; Wang, L.; Xu, C.; Liu, W.; Wang, Y. Anti-oxidative and thrombolytic TMP nitrone for treatment of ischemic stroke. Bioorg. Med. Chem. 16, 8868–8874, 2008.
30.Chen, W-M.; Cheng, C.; Li, B-Z.; Ho, T-L.; Cai, Z-S.; Wang, Y.; Sun, P-H. Py-ridine-4-thiol and amphoteric analogs: novel Pprotection of aryl bromides in strong alkali. Helvetica Chimica Acta. 91, 2062–2068, 2008.
31.Guo, J-L.; Li, B-Z.; Chen, W-M.; Sun, P-H.; Wang, Y. Synthesis of substituted 1 H-pyrrol-2(5 H)-ones and 2(5 H)-furanones as inhibitors of P. aeruginosa biofilm. Lett. Drug Design and Discov. 6, 107–113, 2009.
32.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.
33.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.
34.Zhang, Z.; Jiang, J.; Pei, Y.; Zeng, X.; Wang, Z.; Larrick, J. W.; Wang, Y.Hyp-oglycemic and beta cell protective andrographolide analogue for diabetes treat-ment. J. Translational Med. 7:62, 2009.
35.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.
36.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. Bioo-rg. Med. Chem. 18, 4269–4274, 2010.
37.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. Che-m. Lett. 20, 3844–3847, 2010.
38.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 chr-onic alcohol treated rat and mice model. Chinese Med. 5:36, 2 010.
39.Xu, J.; Lu, Y.; Luo, H.; Huang, S.; Bao, J.; Cai, S.; Wang Y. Homology modeling of α-glucosidase and its interactions with andrograpolide derivatives. Lett. Drug Desi-gn and Discov. 8, 440–451, 2011.
40.Chen, H.; Li, S.; Wu, J.; Jiang, J.; Wang, Y. Pharmacokinetic study of a novel st-roke therapeutic, 2-[[(1,1-dimethylethyl)oxidoimino]methyl]-3,5,6-trimethy-lpyrazine, by a simple HPLC-UV method in rats. Eur. J. Drug. Metab. Ph. 36, 95–101, 2011.
41.Zeng, X.; Liu, X.; Liang, H.; Bian J.; Pei, G.; Dai, H.; Polyak, S. W.; Song, F.; Ma, L.; Wang, Y.; Zhang, Z. Synergistic effect of AL-1 and various antibiotics on the fo-rmation of biofilms and production ofexopolysaccharide and pyocyanin by Pseu-domonas aeruginosa. Antimicrob. Agents Chemother. 55, 3015–3017, 2011.
42.Cui, Q.; Zhang, G.; Yu, P.; Wang, Y. Synthesis and preliminary evaluation of anti-HIV agent AZT prodrug. Yao Xue Xue Bao. 46, 1015–1018, 2011.
43.Lu, X.; Wan, S.; Jiang, J.; Jiang, X.; Yang, W.; Yu, P.; Xu, L.; Zhang, Z.; Zhang, G.; , Zaijun Z.; Shan, L.; Wang, Y. Synthesis and biological evaluations of novel apocynin analogues. Eur. J. Med. Chem. 46, 2691–2698. 2011.
44.Cui, Q.; Zhang, G.; Yu, P.; Wang, Y. Synthesis and preliminary evaluation of an-tiHIV agent AZT prodrug. Acta Pharmaceutica Sinica, 46, 1015–1018, 2011.
45.Yao, H.; Li, S.; Yu, P.; Tang, X.; Jiang, J.; Wang, Y. Reaction characteristics of andrographolide and its analogue AL-1with GSH as a simple chemical simulation of NF-κB Inhibition. Molecules 17, 728–739, 2011.
46.Sun, Y.; Yu.; Zhang, G.; Wang, L.; Zhong, H.; Zhai, Z.; Wang, L.; Wang, Y. Therapeutic effects of tetramethylpyrazine nitrone in rat ischemic stroke models. J. Neurosci. Res. 90, 1662–1669, 2012.
47.Sun, Y.; Zhang, G.; Zhang, Z.; Yu, P.; Zhong, H.; Du, J.; Wang, Y. Novel multi-functional nitrones for treatment of ischemic stroke. Bioorg. Med. Chem. 20, 3939–3945, 2012.
48.Yu, P.; Xia, L.; Zhao, J.; Zhang, G.; Zhang, Z,; Lang, M.; Wang, Y. Synthesis and preliminary anticancer evaluation of 10-hydroxycamptothecin analogs. Biol. Pharm. Bull. 35, 1295–1299, 2012.
49.Ma, Li.; Liu, X.; Liang, H.; Che, Y.; Dai, H.; Yu, K.; Liu, M.; Ma, L.; Yang, C-H.; Song, F.; Wang, Y.; Zhang, L. Molecular targets of 14-alpha-lipoyl andrographolide on quorum sensing in Pseudomonas aeruginosa. Antimicrob. Agents Chemother. 56, 6088–6094, 2012.
50.Cui, G.; Hung, M.; Shan, L.; Lei, S.; Choi, I.; Zhang, Z.; Hoi, M. P.; Yu, P.; Wang, Y.; Lee, S. M. A novel danshensu derivative confers cardioprotection via PI3K/Akt and Nrf2 pathways. Intl. J. Cardio. 168, 1349–1359, 2013.
51.Zhu, Y.; Yu, G.; Zhang, Y.; Xu, Z.; Wang,Y.; Yan, G.;, He, Q. A novel androgra-pholide derivative AL-1 exerts its cytotoxicity on K562 cells through a ROS-dependent mechanism. Proteomics, 13,169–178, 2013.
52.Cui, Q.; Shan, L.; Zhu, H.; Yu, P.; Wang, Y. Synthesis and preliminary evalu-ation of Danshensu derivatives modified at hydroxyl group. J. Intl. Pharm. Res. 40, 795–800, 2013.
53.Yan, G.; Zhou, H.; Wang, Y.; Zhong, Y.; Tan, Z.; Wang, Y.; He, Q. Protective effects of andrographolide analogue AL-1 on ROS-induced RIN-m β cell death by inducing ROS generation. PLoS One, 8(6):e63656. doi: 10.1371, 2013.
54.Talantovaa, M.; Sanz-Blascoa, S.; Zhang. X.; Xia, P.; Waseem Akhtara, M.; Ok-amotoa, S.; Dziewczapolskib, G.; Nakamuraa, T.; Gang, C.; Pratta, A. E.; Kanga, Y-J.; Tua, S.; Molokanovaa, E.; McKerchera, S. R.; Hiresd, A. A.; Sasone, H.; Sto-ufferf, D. G.; Buczynskif, M. W.; Solomong, J.; Michaelc, S.; Powersg, E. T.; Kell-yg, J. W.; Robertsj, A.; Tonga, G.; Fang-Newmeyera, T.; Parkera, J.; Hollanda, E. A.; Zhang, D.; Nakanishia, N.; Chen, H-S, V.; Woloskere, H.; Wang, Y.; Parsonsf, L. H.; Ambasudhana,R.; Masliahc, E.; Heinemannb, S. F.; Piña-Crespoa, J. C.; Lipton, S. A. Aβ induces astrocytic glutamate release, extrasynaptic NMDA receptor activa-tion, and synaptic loss. PNAS, 110, E2518–2527, 2013.
55.Xu, D.; Duan, H.; Du, J.; Zhang, Z.; Cui, W.; Wang, L.; Sun, Y.; Lang, M.; Hoi, P. M.; Han, Y.; Wang, Y.; Lee, S. M. The novel tetramethylpyrazine bis-nitrone (TN-2) protects against MPTP/MPP-induced neurotoxicity via inhibition of mitochondrial de-pendent apoptosis. J. Neuroimmun. Pharmacol. 2013 (advance online DOI 10.1007/s11481-013-9514-0).
56.Guo, B.; Xu, D.; Duan, H.; Du, J.; Zhang, Z.; Lee, S. M.; Wang, Y. Therapeutic effects of multifunctional tetramethylpyrazine nitrone on models of Parkinson’s dis-ease in vitro and in vivo. Biol. Pharm. Bull. 37, 274–285, 2014.
57.Cui, W.; Zhang, Z.; Hu, S.; Mak, S.; Xu, D.; Choi, C.; Wang, Y.; Tsim, K.; Lee, M.; Rong, J.; Han, Y. Sunitinib produces neuroprotective effect via inhibiting nitric oxide overproduction. CNS Neurosci. Ther. 2014 Jan 7. doi: 10.1111/cns.12203.
58.Sun, Y.; Liao, K.; Li, S.; Zhang, Z.; Yu, P.; Wang, Y. Pharmacokinetic analysis of bis-nitrone tetramethylpyrazine (TN-2) in rats and its protein binding in vitro. Lett. Drug Design and Discov. 2014 (advance online).
59.Lang, M.; Yan, R.; Wang, Y.; Yu, P. A selective O- and N-acylation protocol for carbamyl chloride. Chin. J. Org. Chem. 2014 (advance online).
60.Cui, Q.; Chen, Y.; Zhang, M.; Shan, L.; Sun, Y.; Yu, P.; Zhang, G.; Wang, D.; Zhao, Z.; Xu, Q.; Xu, B.; Wang, Y. Design, synthesis and preliminary cardioprote-ctive effect evaluation of Danshensu derivatives. Chem. Biol.&DrugDes. 2014 (advance online).
61.Li, S.; Shan, L.; Zhang, Z.; Li, W.; Liao, K.; Li, S.; Yu, P.; Wang, Y. Pharma-cokinetic and metabolism studies of ADTM, a novel Danshensu derivative confers cardioprotection by HPLC-UV and LC-MS/MS . J. Chromatogr. Sci. 2014 (advance online).
62.Xu, L.; Li, Y.; Wan, S.; Wang, Y.; Yu, P. Apocynin nitrone protects rats from LPS-mediated acute lung injury via inhibition of NADPH oxidase. Intl. Immunophar-macol. 2014 (advance online).
63.Du, E.; Liang, Z.; Xu, L.; Sun, S.; Zhang, G.; Yu, P.; Wang, Y. Synthesis and preliminary biologic activity evaluation of nitric oxide-releasing andrographolide ana-logues. Chem Pharma Bull. 2014 (advance online).
64.Zhang, Z.; Lai, D.; Wang, L.; Pei, Y.; Zhu, L.; Guo, B.; Xu, L.; Sun, Y.; Xu, L.; Zhou, L.; Sun, Y.; Lee, S-M.; Wang, Y. Neuroprotective effects of the androgra-pholide analogue AL-1 in the MPP/MPTP-induced Parkinson’s disease model in vitro and in mice. Pharmacol. Biochem. Be. 2014 (advance online).