簡單介紹

男，博士，教授，博導，工會主席；2010年入選“中山大學卓越人才”計劃；2013年“廣東省優秀碩士學位論文”研究生導師；廣東省藥學會藥物化學專家委員會委員。2003年畢業于中山大學化學與化學工程學院，獲理學博士學位；2004年5月-2005年11月，香港科技大學博士後；2013年6月-2014年6月，美國癌症研究所客座研究員。工作期間分别主持了包括“十一五”國家科技重大專項“重大新藥創制”項目、國家自然科學基金、廣東省自然科學基金等多項基金項目；作為主要完成人分别獲得2010年度廣東省科學技術獎一等獎和2010年高校科學研究優秀成果獎自然科學獎二等獎；發表學術論文90多篇；申請國際專利13項、中國專利9項，成功實施轉讓2項。

研究方向

藥物化學、靶向創新藥物研究

 

招聘信息

本課題組長期招聘有藥物化學、生物化學、藥理學背景的博士後或者專職科研人員。

薪酬待遇：

1. 入職博後子女可免費入讀中山大學附屬幼兒園、小學、初中等。

2. 除國家、省市報酬以及學院補貼外，課題組補貼10萬+/年，總年薪30萬以上（優秀者薪酬可面議）。

 

科研項目

研究興趣：靶向創新藥物研究。

DNA拓撲異構酶（包括Top1和Top2，以及細菌Top3、Gyrase）是DNA轉錄、複制過程必須的酶。在DNA的轉錄、複制過程中，Top斷裂DNA鍊，形成Top-DNA共價複合物；并通過控制旋轉，松散DNA的超螺旋結構，以保證DNA複制過程的順利進行。Top抑制劑可以引起DNA複制損傷，從而殺死細胞，是潛在的抗腫瘤藥物或者抗菌藥物。目前，人Top抑制劑是一大類臨床使用的抗腫瘤藥物或抗菌藥物，例如喜樹堿類藥物、阿黴素類藥物、依托泊苷類藥物及喹諾酮類藥物等。

在部分腫瘤細胞中，高表達DNA修複酶，修複化療藥物所緻的DNA損傷，導緻腫瘤耐藥，例如，酪氨酰DNA磷酸二脂酶（Tyrosyl-DNA Phosphodiesterase，TDP）。TDP包括TDP1和TDP2，分别對應修複由Top1和Top2引起的DNA損傷。高表達TDP的腫瘤細胞對Top抑制劑産生耐藥，這是腫瘤細胞耐藥的一個重要原因。在某些Checkpoint mediator蛋白缺失的腫瘤細胞中，TDP通路是修複DNA損傷的主要通路。因此，TDP抑制劑可增強Top抑制劑的抗腫瘤活性，是一類抗腫瘤增敏劑及耐藥逆轉劑。

本課題組的研究興趣：設計、合成基于該DNA損傷、修複通路的、靶向Top或者TDP的抑制劑，發現創新藥物。

 

近年主持的縱向研究課題：

  1. 氧代兩面針堿類TDP1抑制劑的結構優化、抗耐藥腫瘤活性及其作用機制研究，國家自然科學基金（82173655），2022年1月-2025年12月。

  2. Myrtucommulone類TDP2抑制劑的結構優化、逆轉腫瘤耐藥及其分子機制研究，廣東省自然科學基金（2019A1515011317），2019年10月-2022年10月。

  3. 新機制的Azan 類拓撲異構酶I 抑制劑的設計、合成及抗腫瘤研究，國家自然科學基金（81373257），2014年1月-2017年12月。

  4. 抗MRSA 感染新藥Azanaph-7 的臨床前研究，廣東省重大科技專項（分題No. 2013A022100035），2015年1月-2017年12月。

  5. 中氮茚并喹啉二酮類抗腫瘤先導化合物的發現及其作用機制研究，國家自然科學基金（30801425），2009年1月-2011年12月。

  6. 抗耐藥性病原菌--MRSA感染的候選新藥Azanaph-7的研發， “重大新藥創制”國家科技重大專項（2009ZX09103-042），2009年1月-2010年12月。

  7. IQD類拓撲異構酶I催化抑制劑的設計、合成及抗腫瘤活性研究，廣東省自然科學基金（S2013010015609），2013年10月-2015年10月。

  8. 基于拓撲異構酶I為靶點的Azanaph類抗腫瘤先導物的發現及作用機制研究，廣東省自然科學基金（10151008901000022），2011年1月-2012年12月。

 

論著專利

部分代表作（*為通訊作者）：

  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

 

專利：

  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，張曉茹，王浩文，唐文林，胡德玄，張宇. 一種稠環類化合物及其制備方法和用途. 中國專利申請号：201810827467.1  2018年7月25日. 公布号: CN 110759963A  2020年2月7日.
  4. 安林坤，朱騰偉，楊會，古練權. 一類用于制備抗菌藥物中的化合物及其用途. 中國專利申請号：201610511904.X  2016年6月30日
  5. 安林坤，巫錫偉，吳族平，古練權.溴代中氮茚并喹啉二酮類衍生物及其在制備抗菌藥物中的應用. 中國專利号：ZL 201110040995.0  2012年9月5日.
  6. 古練權, 黃志纾, 劉忠, 張竹林, 鮑雅丹, 安林坤, 黃世亮. 喹啉二酮類衍生物及其在制備抗菌藥物中的應用. 中國專利号：ZL 200610036484.0  2008年12月10日.
  7. 古練權, 杜志雲, 鮑雅丹, 黃志纾, 安林坤, 鄢明, 劉培慶, 潘武賓, 陳新滋. 2, 6-二吡啶烯環己酮衍生物及其在制備抗菌藥物中的應用. 中國專利号: ZL 200610034181.5  2009年1月14日。