药物化学系

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凌勇

作者:金飞     日期:2023-10-17   点击数:3019  

师资介绍

凌勇,男,汉族,19822月生,教授,博士生导师,药物化学系主任

研究方向:

基于肿瘤和炎症疾病的诊断和治疗药物研究

社会学术兼职:

中国药学会会员,中国生物材料学会神经修复材料分会委员,江苏省药学会药物化学专业委员会委员,中国化学会会员,南通市药学会理事会常务理事以及专业委员会主任委员;中国政府奖学金评审专家,江苏省高新技术企业评审专家,江苏省政府采购专家。

基金项目:

1、江苏省重点研发计划项目,基于肿瘤微环境多重响应的β-咔啉类诊疗剂的研究与开发,项目号:BE20216772021.9-2024.1250万,主持。

2、江苏省高等学校自然科学研究重大项目,酶/pH双响应型诊疗剂的分子构建和抗肿瘤转移研究,项目号:20KJA3500022020.10-2023.1030万,主持。

3、中国博士后基金特别支助项目,基于靶向和pH敏感的诊疗剂的设计合成及抗转移机制研究,项目号:2018T1105332018.10-2021.1215万,主持。

4、国家自然科学青年基金,具有多重活性的新型法尼基硫代水杨酸衍生物的合成、抗肿瘤活性及其机制研究,项目号:813026282014.1-2016.1223万,主持。

5、国家自然科学面上项目选择性食欲素1型受体拮抗剂设计合成及对物质成瘾治疗作用研究,项目号:219770582020.1-2023.1266万,参与。

6教育部产学合作协同育人项目,依托计算机辅助药物设计平台开展药学专业人才的创新能力培养研究,项目号:2020021550482020.10-2022.125万,主持。

7、江苏省六大人才高峰高层次人才项目B类,项目号:2014-SWYY-044,具有纳米载药功能的多靶点抗癌核苷前药的研究与开发,2015.1-2017.1210万,主持。

8、中国博士后基金面上项目,一等资助,靶向HDAC和细胞周期相关酶的β咔啉衍生物抗癌活性研究,项目号:2016M5904882016.1-2017.128万,主持。

9南通市科技计划面上项目,项目号:MS12020047,基于酶激活/pH敏感的新型肿瘤诊疗剂的研究与开发,2020.10-2023.910万,主持

10、南通市科技计划面上项目,项目号:MS12018079,基于苄亚基环己烯酮骨架的新型硫氧还原蛋白抑制剂的研究与开发,2019.1-2021.910万,主持。

11、天然药物活性组分与药效国家重点实验室开放性课题,项目号:SKLNMKF-201610,基于HDAC和细胞周期相关酶为靶标的新型β-咔啉衍生物设计、合成及抗癌活性研究,2016.1-2016.125万,主持。

12、江苏省博士后科研资助计划B类,项目号:1601136B2016.7-2018.63万,主持。

13、江苏省自然科学基金,项目号:BK2011389Ras抑制剂的设计、合成、抗癌活性及作用机制的研究,2011.7-2014.68万,主持。

14、南通市科技计划项目,项目号:MS12015060,具有HDAC和细胞周期相关酶双重靶向的新型β-咔啉衍生物设计合成及抗癌机制研究,2016.1-2018.93万,主持。

科研成果:

江苏省“333 人才工程高层次人才培养对象,江苏省双创计划科技副总,江苏省六大人才高峰高层次人才培养对象以及创新团队骨干培养对象,获南通市科技进步二等奖,获得授权发明专利50余项,其中国际专利5项,转让发明专利10余项;在药物化学权威期刊J Med ChemTheranosticsBiosens BioelectronGreen ChemChem Eng JACS Appl Mater InterfacesEur J Med ChemJ Nat Prod等主流刊物发表SCI学术论文100余篇,其中影响因子大于107篇,中科院一区论文20余篇,累积被引用2000余次。指导本科生获得全国大学生药苑论坛创新成果二等奖、江苏省本科毕业设计(论文)一等奖、团队优秀论文,长三角生态绿色一体化示范区大学生创新创业大赛等奖。

代表性论文:

  1. 1. Liu J, Xu Z, Meng C, Wusiman S, Xie X, Wang Y, Xiao F, Gu C, Chen J, Ling CC, Li P, Yuan Z*, Ling Y*. Acidic tumor microenvironment-activatable fluorescent diagnostic probe for the rapid identification and resection of human tumors via spraying. Biosens Bioelectron. 2023, 234:115343. (IF=12.5)

    2. Xu Z, Qian J, Wu H, Meng C, Ding Q, Tao W, Ling CC, Chen J, Li P, Yang Y*, Ling Y*. Novel pH-activatable NIR fluorogenic spray mediated near-instant and precise tumor margins identification in human cancer tissues for surgical resection. Theranostics. 2023;13(13):4497-4511. (IF=12.4)

    3. Jue Ling, Yi Luo, Cheng Sun, Zhangji Dong, Ronghua Wu, Xiaoxuan Tang, Nan Du, Rui Zhu, Shi Chen, Mei Liu, Yan Liu, Yongjun Wang, Xiaosong Gu, Yong Ling*, Yumin Yang*. Live intraoperative diagnosis of hepatic metastasis via HDACs targeting molecular theranostic agent. Chem Eng J. 2021, 406, 126900. (IF=16.744)

    4. Xin Liu*, Ji Liu, Qin Xu, Weizhi Tao, Xudong Xie, Chi Meng, Qinbei Zhou, Yanan Zhang, Yong Ling*. A Versatile Supramolecular Nanoagent for Three-Pronged Boosting Chemodynamic Therapy. J Colloid Interface Sci, 648(2023)994–1005. (IF=9.9)

    5. Meng, C., Xie, X., Qian, J., Tao, W., Wu, H., Ji, D., Gao, G., Wang, R., Ling, C., Liu, X.*, Ling, Y*. TME-targeting nano-theranostic agent for NIR fluorescence diagnosis and O2-economized PDT-based multimodal synergistic therapy. Materials & Design, 2023, 233, 112251. (IF=8.4)

    6. Ling, C. C.*, Sun, T., Chen, F., Wu, H., Tao, W., Xie, X., Ji, D., Gao, G., Chen, J., Ling, Y*., Zhang, Y*. Precise tumor delineation in clinical tissues using a novel acidic tumor microenvironment activatable near-infrared fluorescent contrast agent. Analytica Chimica Acta, 2023, 1279:341815.

    7. Zhongyuan Xu, Jianqiang Qian, Chi Meng, Yun Liu, Qian Ding, Hongmei Wu, Peng Li, Fansheng Ran, Gong-Qing Liu, Yunyun Wang*, Yong Ling*. TME-targeting theranostic agent uses NIR tracking for tumor diagnosis and surgical resection and acts as chemotherapeutic showing enhanced efficiency and minimal toxicity. Theranostics 2022, 12(6)2535-2548. (IF=12.4)

    8. Qian J, Xu Z, Meng C, Liu Y, Wu H, Wang Y, Yang J, Zheng H, Ran F*, Liu GQ*, Ling Y*. Redox-Activatable Theranostic Co-Prodrug for Precise Tumor Diagnosis and Selective Combination Chemotherapy. J Med Chem. 2022, 65(15): 10393-10407. (IF=7.3)

    9. Liu X*,#, Liu J#, Meng C, Zhu P, Liu X, Qian J, Ling S, Zhang Y, Ling Y*. Pillar[6]arene-Based Supramolecular Nanocatalysts for Synergistically Enhanced Chemodynamic Therapy by the Intracellular Cascade Reaction. ACS Appl Mater Interfaces. 2021, 13(45):53574-53585. (IF=10.383)

    10. Gongqing Liu*, Chenfan Zhou, Yunqian Zhang, Wei Yi, Pengfei Wang, Ji Liu, Yong Ling*. Visible-light-induced intermolecular aminoselenation of alkenes, Green Chemistry. 2021, 23, 9968-9973. (IF=11.034)

    11. Gongqing Liu*, Wei Yi, Pengfei Wang, Ji Liu, Meng Ma, Dayun Hao, Liang Ming, Yong Ling*. Visible-light-induced oxidative coupling of vinylarenes with diselenides leading to α-aryl and α-alkyl selenomethylketones, Green Chemistry, 2021, 23: 1840-1846. (IF=11.034)

    12. Ran F, Xie X, Wu Q, Wu H, Liu Y, Tao W, Sun Y, Wang R, Zhang Y*, Ling Y*. Development of novel hydrazidoarylaminopyrimidine-based BTK/FLT3 dual inhibitors with potent in vivo anti-hematological malignancies effects. Eur J Med Chem. 2023, 245(Pt 1):114913.

    13. Ran F, Liu Y, Zhu J, Deng X, Wu H, Tao W, Xie X, Hu Y, Zhang Y, Ling Y. Design, synthesis and pharmacological characterization of aminopyrimidine derivatives as BTK/FLT3 dual-target inhibitors against acute myeloid leukemia. Bioorg Chem. 2023, 134:106479.

    14. Zhu P, Qian J, Xu Z, Meng C, Zhu W, Ran F, Zhang W, Zhang Y*, Ling Y*. Overview of piperlongumine analogues and their therapeutic potential. Eur J Med Chem. 2021, 220:113471.

    15. Xin Liu#,*; Chi Meng#; Guiqing Ji; Ji Liu; Peng Zhu; Jianqiang Qian; Shun-Xing Zhu*; Yanan Zhang; Yong Ling*; Tumor microenvironment- activatable boolean logic supramolecular nanotheranostics based on pillar[6]arene for tumor hypoxia imaging and multimodal synergistic therapy, Materials Chemistry Frontiers, 2021, 5: 5846-5856. (IF=8.683)

    16. Li B, Yang Y, Wang Y, Zhang J, Ding J, Liu X, Jin Y, Lian B, Ling Y*, Sun C*. Acetylation of NDUFV1 induced by a newly synthesized HDAC6 inhibitor HGC rescues dopaminergic neuron loss in Parkinson models. iScience. 2021, 24(4): 102302.

    17. Liu J#, Liu X#, Qian J, Meng C, Zhu P, Hang J, Wang Y, Xiong B, Qiu X, Zhu W, Yang Y, Zhang Y*, Ling Y*. Development of pH/Glutathione-Responsive Theranostic Agents Activated by Glutathione S-Transferase π for Human Colon Cancer. J Med Chem2020, 63(17):9271-9283. (IF=7.446)

    18. Qiu X*, Li Y, Zhou L, Chen P, Li F, Zhang Y, Ling Y*. Nickel(II)-Catalyzed Borylation of Alkenyl Methyl Ethers via C-O Bond Cleavage. Org Lett2020, 22(16):6424-6428.

    19. Qian J#, Xu Z#, Meng C, Liu J, Hsu PL, Li Y, Zhu W, Yang Y, Morris-Natschke SL, Lee KH*, Zhang Y*, Ling Y*. Design and synthesis of benzylidenecyclohexenones as TrxR inhibitors displaying high anticancer activity and inducing ROS, apoptosis, and autophagy. Eur J Med Chem2020, 204: 112610.

    20. Yong Ling*, Chenjun Xu,Lin Luo,Jingyi Cao,Jiao Feng,Yu Xue,Qing Zhu,CaoyunJu,Fengzhi Li, Yihua Zhang, Yanan Zhang, Xiang Ling. Novel β-Carboline/Hydroxamic Acid Hybrids Targeting Both Histone Deacetylase and DNA Display High Anticancer Activity via Regulation of the P53 Signaling Pathway. J Med Chem2015, 58(23), 92149227.

    21. Meng C, Qian J, Xu Z, Liu J, Shan W, Zhu P, Zhu W, Miao J, Ling CC*, Ling Y*. Efficacy of novel methylenecyclohexenone derivatives as TrxR inhibitors in suppressing the proliferation and metastasis of human cancer cells. Bioorg Chem. 2020, 105:104360.

    22. Zhu P, Qian J, Xu Z, Meng C, Liu J, Shan W, Zhu W, Wang Y, Yang Y, Zhang W, Zhang Y*, Ling Y*. Piperlonguminine and Piperine Analogues as TrxR Inhibitors that Promote ROS and Autophagy and Regulate p38 and Akt/mTOR Signaling. J Nat Prod. 2020, 83(10):3041-3049. 

    23. Yong Ling*, Weijie Gao,Changchun Ling, LiuJi,Jianqiang Qian, Chi Meng, Sicun Liu, Huiling Gan, Hongmei Wu, Jinhua Tao,Hong Dai*, Yanan Zhang*. β-Carboline and N-hydroxycinnamamide hybrids as anticancer agents for drug-resistant hepatocellular carcinoma. Eur J Med Chem. 2019, 168, 515-526. 

    24. Dai H, Huang M, Qian J, Liu J, Meng C, Li Y, Ming G, Zhang T, Wang S, Shi Y, Yao Y, Ge S, Zhang Y, Ling Y*. Excellent antitumor and antimetastatic activities based on novel coumarin/pyrazole oxime hybrids. Eur J Med Chem. 2019, 166, 470-479. 

    25. Yong Ling, Qiuxing Yang, Yuning Teng, Shi Chen, Weijie Gao, Jing Guo, Peiling Hsu, Yue Liu, Susan L. Morris-Natschke, Chinchuan Hung, Kuohsiung Lee. Development of novel amino-quinoline-5,8-dione derivatives as NAD(P)H: quinone oxidoreductase 1 (NQO1) inhibitors with potent antiproliferative activities. Eur. J. Med. Chem. 2018, 154, 199-209. 

    26. Yong Ling, Jing Guo, Qiuxing Yang, Peng Zhu, Jiefei Miao, Weijie Gao, Yanfu Peng, Jiaying Yang, Kun Xu, Biao Xiong, Gongqing Liu, Jinhua Tao, Lin Luo, Qing Zhu, Yanan Zhang. Development of Novel β-carboline-based hydroxamate derivatives as HDAC inhibitors with Antiproliferative and Antimetastatic Activities in Human Cancer cells. Eur. J. Med. Chem. 2018, 144, 398-409. 

    27. Hong Dai, Shushan Ge, Jin Guo, Shi Chen, Meiling Huang, Jiaying Yang, Siyu Sun, Yujun Shi, Yong Ling*. Development of novel bis-pyrazole derivatives as antitumor agents with potent apoptosis induction effects and DNA damage. Eur. J. Med. Chem. 2018, 143, 1066–1076. 

发明专利:

1. 凌勇杨宇民,李鹏,钱建强,孟迟,张延安,许中原,丁倩,缪道鑫,张雨婷;N,N-二苯基氨基修饰的β-咔啉吲哚鎓盐、制备方法与应用,专利授权号:2021110305364

2. Ling, Yong; Liu, Ji; Liu, Xin; Ling, Changchun; Zhang, Yanan; Qian, Jianqiang; Meng, Chi; Hang, Jiaying; Chen, Sumeng; PH/glutathione-responsive β-carbolines/cycloketene derivatives and their preparation and application, 2020-10-16, PCT/CN2020/121436, AU2020356793.

3. Ling, Yong; Miao, Jiefei; Ling, Changchun; Liu, Xin; Li, Yangyang; Qian, Jianqiang; Meng, Chi; Xie, Xudong; Wu, Hongmei; Zhang, Yirong. The preparation methods and medical applications of 6-benzylidene-2-(phenylethynyl) cyclohexenone derivatives, PCT/CN2020/111184, AU2020387494.

4. Ling, Yong et al; Phenylallyl cyclohexenone derivatives and their preparation method and applicationPCT/CN2020/076878, AU2020213346.

5. 凌勇,刘季,刘昕,凌长春,张延安,钱建强,孟迟,杭佳颖,陈苏蒙,基于pHGSH双重响应的β-咔啉-环烯酮衍生物及其用途,专利授权号:2019112566037

6. 凌勇,郭靖,高伟杰,黄金华,张海健,杨秋星,陈实,刘季,刘越,一类喹啉醌衍生物及制备方法和用途,专利授权号:201810096983

7. 凌勇,彭炎福,熊彪,黄金华,汪莹莹,陈实,钱建强,明古旭,靶向癌细胞高水平ROS的吉西他滨-芳香氮芥缀合物的制备方法和医药用途,授权时间:2020.10.27,专利授权号:201810126637

8. 凌勇,杨圣菊,张延安,刘季,凌长春,李洋阳,刘思群,贾启新,明古旭,吴红梅,苯基亚烯丙基环己烯酮衍生物及制备方法和用途,授权时间:2020.9.15,专利授权号:2019102237404

9. 凌勇,缪捷飞,凌长春,刘昕,李洋阳,钱建强,孟迟,谢旭东,吴红梅,张逸蓉,6-苄亚基-2-芳基乙炔基环己烯酮衍生物及其制备方法和医药用途,授权时间:2020.9.22,专利授权号:2019111329551

10. 凌勇,苏星,彭炎福,郭靖,刘季,朱鹏,杨韬,徐启兵,黄海英,苄亚基环己烯酮衍生物及其制备方法和医药用途,授权时间:2020.4.10,中国,专利授权号:2016111067131

11. 凌勇,缪捷飞,徐启兵,冯娇,朱鹏,刘季,王婷婷,葛翔,梁姗姗,靶向CDKDNAβ 咔啉衍生物及其制备方法和医药用途,授权时间:2018.2.2,中国,专利授权号:2016109117895

12. 凌勇,陈忠平,鞠曹云,许伯慧,吴园园,杨韬,徐启兵,黄海英。NO供体型的吉西他滨/FTA/呋咱缀合物及制备方法和用途,授权时间:2017.7.21,中国,专利授权号:2015101188667

13. 凌勇,杨宇民,李祥华,王成牛,张海健,吴园园,徐启宾,冯娇,苯磺酰基呋咱修饰的吉西他滨衍生物及其制备方法和用途,授权时间:2017.11.17,中国,专利授权号:2015100568616

14. 凌勇,杨宇民、张洁、王志强、王雪敏、赵颖。含有β-咔啉-3-酰亚肼基的新型HDAC抑制剂及其制备方法和医药用途,授权时间:2016.4.13,中国,专利授权号:201410057931.5

15. 凌勇,杨宇民,李祥华,赵颖,陈娟,王雪敏,吴彩霞。具有HDAC抑制活性的β-咔啉类衍生物及制备方法和用途,授权时间:2016.4.13,中国,专利授权号:201410058342.9

16. 凌勇,王志强,吴彩霞,徐晨俊,王雪敏,李祥华,赵颖,欧云淘,吴婷。法尼基硫醚取代的查尔酮衍生物及制备方法和用途,授权时间:2016.4.13,中国,专利授权号:2014104229999

17. 凌勇,王新杨,王志强,王雪敏,李祥华,徐晨俊,陈娟,陈悦,夏超。含有查尔酮骨架的法尼基硫代水杨酸类似物及制备方法和用途,授权时间:2016.4.13,中国,专利授权号:201410422427

18. 凌勇,杨宇民、吴彩霞、王志强、王雪敏、赵颖、陈悦。苯丙烯酸类法尼基硫代水杨酸衍生物、其制备方法及其医药用途,授权时间:2016.1.20,中国,专利授权号:201410032704.7

19. 凌勇,杨宇民、王新杨、王志强、丰楠楠、郭益冰、王雪敏、颜森森。法尼基硫代水杨酸-核苷缀合物、其制备方法及其医药用途,授权时间:2015.9.9,中国,专利授权号:ZL201310407846.2

凌勇,杨宇民、郭益冰、王志强、吴彩霞、王雪敏、颜森森、陈悦。含有羟肟酸的β-咔啉类衍生物及其制备方法和医药用途,授权时间:2015.6.3,中国,专利授权号:201310248832.0