简单介绍

男,博士,教授,博导。2010年入选“中山大学卓越人才”计划;中山大学教学督导团督导;2013年“广东省优秀硕士学位论文”研究生导师;广东省药学会药物化学专家委员会委员;《药学研究》及Hans《药物化学》编委。2003年毕业于中山大学化学与化学工程学院,获理学博士学位;20045-200511月,香港科技大学博士后;20136-20146月,美国癌症研究所客座研究员。工作期间分别主持了包括十一五国家科技重大专项重大新药创制项目、国家自然科学基金、广东省自然科学基金等多项基金项目;作为主要完成人分别获得2010年度广东省科学技术奖一等奖和2010年高校科学研究优秀成果奖自然科学奖二等奖;在国内外重要学术杂志上发表SCI论文50多篇;获得中国授权专利5项,申请美国专利2项。

研究方向

药物化学、有机化学

科研项目

研究兴趣:靶向创新药物研究。

DNA拓扑异构酶(包括Top1Top2,以及细菌Top3Gyrase)是DNA转录、复制过程必须的酶。在DNA的转录、复制过程中,Top断裂DNA链,形成Top-DNA共价复合物;并通过控制旋转,松散DNA的超螺旋结构,以保证DNA复制过程的顺利进行。Top抑制剂可以引起DNA复制损伤,从而杀死细胞,是潜在的抗肿瘤药物或者抗菌药物。目前,人Top抑制剂是一大类临床使用的抗肿瘤药物,例如喜树碱类药物、阿霉素类药物、依托泊苷类药物等;另外,细菌的Top抑制剂是一大类临床使用的抗菌药物,例如喹诺酮类药物。

在部分肿瘤细胞中,高表达DNA修复酶——酪氨酰DNA磷酸二脂酶(Tyrosyl-DNA PhosphodiesteraseTDP)。TDP包括TDP1TDP2,分别对应修复由Top1Top2引起的DNA损伤。高表达TDP的肿瘤细胞对Top抑制剂产生耐药,这是肿瘤细胞耐药的一个重要原因。在某些Checkpoint mediator蛋白缺失的肿瘤细胞中,TDP通路是修复DNA损伤的主要通路。因此,TDP抑制剂可增强Top抑制剂的抗肿瘤活性,是一类抗肿瘤增敏剂及耐药逆转剂。

本课题组的研究兴趣是设计、合成基于该DNA损伤、修复通路的、靶向Top或者TDP的抑制剂,发现创新药物。

 

近年主持的纵向研究课题:

  1. 新机制的Azan 类拓扑异构酶I 抑制剂的设计、合成及抗肿瘤研究,国家自然科学基金(81373257),20141-201712月。

  2. MRSA 感染新药Azanaph-7 的临床前研究,广东省重大科技专项(分题No. 2013A022100035),20151-201712月。

  3. 中氮茚并喹啉二酮类抗肿瘤先导化合物的发现及其作用机制研究,国家自然科学基金(30801425),20091-201112月。

  4. 抗耐药性病原菌--MRSA感染的候选新药Azanaph-7的研发, 重大新药创制国家科技重大专项(2009ZX09103-042),20091-201012月。

  5. MRSA感染新药Azanaph-7的临床前研究,广东省重大科技专项(2013A022100035)子课题,20151-201712月。

  6. IQD类拓扑异构酶I催化抑制剂的设计、合成及抗肿瘤活性研究,广东省自然科学基金(S2013010015609),201310-201510月。

  7. 基于拓扑异构酶I为靶点的Azanaph类抗肿瘤先导物的发现及作用机制研究,广东省自然科学基金10151008901000022),20111-201212月。

 

论著专利

部分代表作(*为通讯作者):

  1. Xiao-Ru Zhang, Hao-Wen Wang, Wen-Lin Tang, Yu Zhang, Hui Yang, De-Xuan Hu, Azhar Ravji, Christophe Marchand, Evgeny Kiselev, Kwabena Ofori-Atta, Keli Agama, Yves Pommier,* Lin-Kun An*. Discovery, Synthesis, and Evaluation of Oxynitidine Derivatives as Dual Inhibitors of DNA Topoisomerase IB (TOP1) and Tyrosyl-DNA Phosphodiesterase 1 (TDP1), and Potential Antitumor Agents. J. Med. Chem. 2018, 61, 9908-9930. Cover article. 2018, 61, 9908-JMC-Discovery of Oxynitidine Derivatives as Dual Inhibitors of TOP1 and TDP1.pdf
  2. Le-Mao Yu, Zhu Hu, Yu Chen, Azhar Ravji, Sophia Lopez, Caroline B. Plescia , Qian Yu, Hui Yang, Monica Abdelmalak, Sourav Saha, Keli Agama, Evgeny Kiselev, Christophe Marchand, Yves Pommier, Lin-Kun An*. Synthesis and structure-activity relationship of furoquinolinediones as inhibitors of Tyrosyl-DNA phosphodiesterase 2 (TDP2). Eur. J. Med. Chem. 2018, 151, 777-796.  2018, 151, 777-EJMC-Synthesis and SAR of furoquinolinediones.pdf
  3. Qian Yu, Hui Yang, Teng-Wei Zhu, Le-Mao Yu, Jian-Wen Chen, Lian-Quan Gu, Zhi-Shu Huang, Lin-Kun An*. Synthesis, cytotoxicity and structure-activity relationship of indolizinoquinolinedione derivatives as DNA topoisomerase IB catalytic inhibitors. Eur. J. Med. Chem. 2018, 152, 195-207. 2018, 152, 195-EJMC--Synthesis, cytotoxicity and SAR indolizinoquinolinedione.pdf
  4. Hui Yang, Hao-Wen Wang, Teng-Wei Zhu, Le-Mao Yu, Jian-Wen Chen, Lu-Xia Wang, Lei Shi, Ding Li, Lian-Quan Gu, Zhi-Shu Huang, Lin-Kun An*. Syntheses and antibacterial activity of soluble 9-bromo substituted indolizinoquinoline-5,12-dione derivatives. Eur. J. Med. Chem. 2017, 127, 166-173. 2017, 1127, 166-EJMC- Syntheses and antibacterial activity of soluble 9-bromo substituted indolizinoquinoline-5,12-dione derivatives.pdf
  5. Xu-Jie Qin, Qian Yu, Huan Yan, Afsar Khan, Mi-Yan Feng, Pan-Pan Li, Xiao-Jiang Hao, Lin-Kun An,* Hai-Yang Liu*. Meroterpenoids with Antitumor Activities from Guava (Psidium guajava). J. Agric. Food Chem. 2017, 65, 4993−4999. 2017, 65, 4993−JAFC-Meroterpenoids with Antitumor Activities from Guava.pdf
  6. Le-Mao Yu, Xiao-Ru Zhang, Xiao-Bing Li, Yuan Yang, Hong-Yu Wei, Xi-Xin He, Lian-Quan Gu, Zhi-Shu Huang, Yves Pommier, Lin-Kun An*. Synthesis and biological evaluation of 6-substituted indolizinoquinolinediones as catalytic DNA topoisomerase I inhibitors. Eur. J. Med. Chem. 2015, 101, 525-533.2015, 101, 525-EJMC-Synthesis and biological evaluation of 6-substituted indolizinoquinolinediones as catalytic Top1 inhibitors.pdf 

  7. Yang Ding, Qiong Wu, Kangdi Zheng, Linkun An*, Xiaoying Hu, Wenjie Mei*. Imaging of the nuclei of living tumor cells by novel ruthenium(II) complexes coordinated with 6-chloro-5-hydroxylpyrido[3,2-a]phenazine. RSC Adv. 2015, 5, 63330-63337.

  8. Da-Li Zhang, Li-Yan Zhou, Jun-Min Quan, Wei Zhang, Lian-Quan Gu, Zhi-Shu Huang, Lin-Kun An*. Oxygen-Insertion of o-Quinone under Catalytic Hydrogenation Conditions. Org. Lett. 2013, 15 (6), 1162–1165. OL 2013, 15, 1162–Oxygen Insertion of o-Quinone under Catalytic Hydrogenation Conditions.pdf 

  9. Lin-Kun An*, Run-Lin Li, Ying-Lin Zuo, Lian-Quan Gu. Solvent-Free Thermocyclization of the Unactivated Linear Gramicidin S Precursor and Analogues. Org. Lett. 2011, 13 (1), 34-37. OL 2011,13, 34-Solvent-Free Thermocyclization of the Unactivated Linear Gramicidin S Precursor and Analogues.pdf 

  10. Wei Zhang, Qiu-Mao Chen, Xi Cheng, Ning Wu, Guo-Bin Yi, Ding Li, Jia-Heng Tan, Zhi-Shu Huang, Lian-Quan Gu, Lin-Kun An*. Syntheses, spectroscopic characterization and application to DNA determination of novel fluorescent pyridophenazine derivatives. Dyes Pigments 2013, 99, 82-89. Dyes Pigments 2013,99,82-Syntheses, spectroscopic characterization and application to DNA determination of novel fluorescent pyridophenazine derivatives.pdf 

  11. Zu-Ping Wu, Xi-Wei Wu, Ting Shen, Yan-Ping Li, Xi Cheng, Lian-Quan Gu, Zhi-Shu Huang, Lin-Kun An*. Synthesis, acetylcholinesterase and butyrylcholinesterase inhibitory activities of 7-alkoxyl substituted indolizinoquinoline-5,12-dione derivatives. Arch. Pharm. Chem. Life Sci. 2012, 345(3), 175-184. Arch. Pharm. Chem. Life Sci. 2012, 345, 175-Synthesis and Acetylcholinesterase and Butyrylcholinesterase Inhibitory Activities of 7-Alkoxyl Substituted Indolizinoquinoline-5,12-dione Derivatives.pdf 

  12. Xi-Wei Wu, Zu-Ping Wu, Lu-Xia Wang, Hong-Bin Zhang, Jian-Wen Chen, Wei Zhang, Lian-Quan Gu, Zhi-Shu Huang, Lin-Kun An*. Synthesis, antimicrobial activity and possible mechanism of action of 9-bromo-substituted indolizinoquinoline-5,12-dione derivatives. Eur. J. Med. Chem. 2011, 46 (9), 4625-4633. EJMC 2011,46,4625-Synthesis, antimicrobial activity and possible mechanism of action of 9-bromo-substituted indolizinoquinoline-5,12-dione derivatives.pdf 

  13. Ning Wu, Xi-Wei Wu, Keli Agama, Yves Pommier, Jun Du, Ding Li, Lian-Quan Gu*, Zhi-Shu Huang, Lin-Kun An*. A Novel DNA Topoisomerase I Inhibitor with Different Mechanism from Camptothecin Induces G2/M Phase Cell Cycle Arrest to K562 Cells. Biochemistry 2010, 49, 10131–10136. Biochem 2010,49,10131-A Novel DNA Topoisomerase I Inhibitor with Different Mechanism from Camptothecin Induces G2M Phase Cell Cycle Arrest to K562 Cells.pdf 

  14. De-Qing Shen, Zu-Ping Wu, Xi-Wei Wu, Zeng-Yun An, Xiang-Zhang Bu, Lian-Quan Gu, Zhi-Shu Huang, Lin-Kun An*. Synthesis and Antiproliferative Activity of Indolizinophthalazine-5,12-dione Derivatives, DNA Topoisomerase IB Inhibitors. Eur. J. Med. Chem. 2010, 45, 3938-3942. EJMC 2010-Synthesis and antiproliferative activity of indolizinophthalazine-5,12-dione derivatives, DNA topoisomerase IB inhibitors.pdf 

  15. De-Qing Shen, Ning Wu, Yan-Ping Li, Zu-Ping Wu, Hong-Bin Zhang, Zhi-Shu Huang, Lian-Quan Gu, Lin-Kun An*. Design, synthesis, and cytotoxicity of indolizinoquinoxaline-5,12-dione derivatives, novel DNA topoisomerase IB inhibitors. Aust. J. Chem. 2010, 63, 1116-1121. Aust. J. Chem. 2010, 63, 1116–1121.pdf 

  16. Yu Cheng, Lin-Kun An*, Ning Wu, Xiao-Dong Wang, Xian-Zhang Bu, Zhi-Shu Huang and Lian-Quan Gu*. Synthesis, cytotoxic activities and structure–activity relationships of topoisomerase I inhibitors: indolizinoquinoline-5,12-dione derivatives. Bioorg. Med. Chem. 2008, 16, 4617–46252008-BMC-Synthesis cytotoxic activities and structure–activity relationships of topoisomerase I inhibitors.pdf

 

专利:

  1. Linkun An, Christophe Marchand, Yves Pommier. Furoquinolinediones as Inhibitors of TDP2. International Application Number: PCT/US 2016/012672, 8 Jan 2016. International Publication Number: WO 2016/112304 A1, 14 Jul 2016.

  2. 安林坤,朱腾伟,杨会,古练权. 一类用于制备抗菌药物中的化合物及其用途. 中国专利申请号:201610511904.X  2016630

  3. 安林坤,巫锡伟,吴族平,古练权.溴代中氮茚并喹啉二酮类衍生物及其在制备抗菌药物中的应用. 中国专利号:ZL 201110040995.0  201295.

  4. 古练权, 黄志纾, 刘忠, 张竹林, 鲍雅丹, 安林坤, 黄世亮. 喹啉二酮类衍生物及其在制备抗菌药物中的应用. 中国专利号:ZL 200610036484.0  20081210.

  5. 古练权, 杜志云, 鲍雅丹, 黄志纾, 安林坤, 鄢明, 刘培庆, 潘武宾, 陈新滋. 2, 6-二吡啶烯环己酮衍生物及其在制备抗菌药物中的应用. 中国专利号: ZL 200610034181.5  2009114日。