安林坤

安林坤

教授

研究领域：靶向创新药物研究

办公电话： 020-39943413

联系邮箱： lssalk@mail.sysu.edu.cn

简单介绍

男，博士，教授，博导，工会主席；2010年入选“中山大学卓越人才”计划；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。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；2004年5月-2005年11月，香港科技大学博士后；2013年6月-2014年6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；发表学术论文90多篇；申请国际专利13项、中国专利9项，成功实施转让2项。

 

研究方向

药物化学、靶向创新药物研究

 

招聘信息

本课题组长期招聘有药物化学、生物化学、药理学背景的博士后或者专职科研人员。

薪酬待遇：

1. 入职博后子女可免费入读中山大学附属幼儿园、小学、初中等。

2. 除国家、省市报酬以及学院补贴外，课题组补贴10万+/年，总年薪30万以上（优秀者薪酬可面议）。

 

科研项目

研究兴趣：靶向创新药物研究。

DNA拓扑异构酶（包括Top1和Top2，以及细菌Top3、Gyrase）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或抗菌药物，例如喜树碱类药物、阿霉素类药物、依托泊苷类药物及喹诺酮类药物等。

在部分肿瘤细胞中，高表达DNA修复酶，修复化疗药物所致的DNA损伤，导致肿瘤耐药，例如，酪氨酰DNA磷酸二脂酶（Tyrosyl-DNA Phosphodiesterase，TDP）。TDP包括TDP1和TDP2，分别对应修复由Top1和Top2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：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. 氧代两面针碱类TDP1抑制剂的结构优化、抗耐药肿瘤活性及其作用机制研究，国家自然科学基金（82173655），2022年1月-2025年12月。
  2. Myrtucommulone类TDP2抑制剂的结构优化、逆转肿瘤耐药及其分子机制研究，广东省自然科学基金（2019A1515011317），2019年10月-2022年10月。
  3. 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），2014年1月-2017年12月。
  4. 抗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），2015年1月-2017年12月。
  5. 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），2009年1月-2011年12月。
  6. 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），2009年1月-2010年12月。
  7. 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），2013年10月-2015年10月。
  8. 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），2011年1月-2012年12月。

 

论著专利

部分代表作（*为通讯作者）：

  1. De-Xuan Hu, Wen-Lin Tang, Yu Zhang, Hao Yang, Wenjie Wang, Keli Agama, Yves Pommier*, Lin-Kun An*. Synthesis of Methoxy‑, Methylenedioxy‑, Hydroxy‑, and Halo-Substituted Benzophenanthridinone Derivatives as DNA Topoisomerase IB (TOP1) and Tyrosyl-DNA Phosphodiesterase 1 (TDP1) Inhibitors and Their Biological Activity for Drug-Resistant Cancer. J. Med. Chem. 2021, https://doi.org/10.1021/acs.jmedchem.1c00318 .  acs.jmedchem.1c00318.pdf
  2. Hao Yang, Xiao-Qing Zhu, Wenjie Wang, Yu Chen, Zhu Hu, Yu Zhang, De-Xuan Hu, Le-Mao Yu, Keli Agama, Yves Pommier, Lin-Kun An*. The synthesis of furoquinolinedione and isoxazoloquinolinedione derivatives as selective Tyrosyl-DNA phosphodiesterase 2 (TDP2) inhibitors. Bioorg. Chem. 2021, 111, 104881. 2021%2C%20111%2C%20104881-BC-%20The%20synthesis%20of%20furoquinolinedione%20and%20isoxazoloquinolinedione%20as%20TDP2%20inhibitors.pdf
  3. Long-Gao Xiao, Yu Zhang, Hong-Li Zhang, Ding Li, Qiong Gu, Gui-Hua Tang, Qian Yu*, Lin-Kun An*. Spiroconyone A, a new phytosterol with spiro [5,6] ring system from Conyza japonica. Org. Biomol. Chem. 2020, 18 (27), 5063-5268. Front Cover article. 2020%2C%2018%2C%205063-OBC-Spiroconyone%20A.pdf
  4. Hong-Li Zhang, Yu Zhang, Xue-Long Yan, Long-Gao Xiao, De-Xuan Hu, Qian Yu*, Lin-Kun An*. Secondary Metabolites from Isodon ternifolius (D. Don) Kudo and Their Anticancer Activity As DNA Topoisomerase IB and Tyrosyl-DNA Phosphodiesterase 1 inhibitors. Bioorg. Med. Chem. 2020, 28(11), 115527. 2020%2C%2028%2C%20115527-BMC-Secondary%20metabolites%20from%20Isodon%20ternifolius%20Kudo.pdf
  5. Long-Gao Xiao, Si-Chen Zhang, Yu Zhang, Lu Liu, Hong-Li Zhang, Qian Yu*, Lin-Kun An*. Sesquiterpenoids from the aerial parts of Conyza japonica and their inhibitory activity against nitric oxide production. Fitoterapia 2020, 142, 104473. 2020%2C%20142%2C%20104473-Fitoterapia-Sesquiterpenoids%20from%20the%20aerial%20parts%20of%20Conyza%20japonica.pdf
  6. Chong-Fa Lai, Wei-Bin Xiao, Hua-Cheng Yan, Hui Yang, Lu-Xia Wang, Hui Guan, Qiu-Ju Peng, Zhi-Rong Deng, Jian-Wen Chen, Lin-Kun An*, Lei Shi*. ZTW-41, a potent indolizinoquinoline-5,12-dione derivative against drug-resistant Staphylococci and Enterococci bacteria. Microb. Drug Resist. 2020, 26 (2), 100-109. 2020%2C%2026%2C%20100-Microb%20Drug%20Resist-ZTW-41%2C%20a%20potent%20derivative%20against%20MRSA.pdf
  7. Wen-Lin Tang, Yu Zhang, De-Xuan Hu, Hui Yang, Qian Yu, Jian-Wen Chen, Keli Agama, Yves Pommier, Lin-Kun An*. Synthesis and biological evaluation of 5-aminoethyl benzophenanthridone derivatives as DNA topoisomerase IB inhibitors. Eur. J. Med. Chem. 2019, 178, 81-92. 2019%2C%20178%2C%2081-EJMC-Synthesis%20and%20biological%20evaluation%20of%205-aminoethyl%20benzophenanthridone.pdf
  8. Zhan-Yong Tang#, Yu Zhang#, Yu-Ting Chen, Qian Yu, Lin-Kun An*. The first small fluorescent probe as Tyrosyl-DNA phosphodiesterase 1 (TDP1) Substrate. Dyes Pigments 2019, 169, 45-50. 2019%2C%20169%2C%2045-Dyes%20and%20Pigments-The%20first%20small%20fluorescent%20probe%20as%20TDP1%20substrate.pdf
  9. Qian Yu, Yu Chen, Hui Yang, Keli Agama, Yves Pommier, Lin-Kun An*. The antitumor activity of CYB-L10, a human topoisomerase IB catalytic inhibitor. J. Enzym. Inhib. Med. Chem. 2019, 34(1), 818-822. 2019%2C%2034%2C%20818-J%20Enzym%20Inhib%20Med%20Chem-The%20antitumor%20activity%20of%20CYB-L10.pdf
  10. 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
  11. 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
  12. 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
  13. 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
  14. 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
  15. 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 
  16. 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.
  17. 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 
  18. 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 
  19. 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 
  20. 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 
  21. 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 
  22. 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 
  23. 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 
  24. 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 
  25. 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, 4617–4625. 2008-BMC-Synthesis cytotoxic activities and structure–activity relationships of topoisomerase I inhibitors.pdf

 

专利：

  1. Lin-Kun An, Xiaoru Zhang, Haowen Wang, Yves Georges Pommier, Evgeny A. Kiselev, Azhar Ali Ravji, Keli Kisseh Agama. Oxynitidine derivatives useful as inhibitors of topoisomerase IB (Top1) and tyrosyl-DNA phosphodiesterase 1 (Tdp1). International Application Number: PCT/US2019043357  25 July 2019; International Publication Number:: WO 2020/023700 A2,  30 Jan. 2020.
  2. 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.
  3. 安林坤，张晓茹，王浩文，唐文林，胡德玄，张宇. 一种稠环类化合物及其制备方法和用途. 中国专利申请号：201810827467.1  2018年7月25日. 公布号: CN 110759963A  2020年2月7日.
  4. 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  2016年6月30日
  5. 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  2012年9月5日.
  6. 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  2008年12月10日.
  7. 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  2009年1月14日。