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化学进展 2018, Vol. 30 Issue (6): 831-846 DOI: 10.7536/PC171212 前一篇   后一篇

• 综述 •

作为抗肿瘤药物的小分子四价铂

谭晓晓1,2, 李国帅1, 王庆鹏1*, 王炳全1, 李大成1,2*, 王鹏3   

  1. 1. 聊城大学生物制药研究院 聊城 252059;
    2. 聊城大学化学化工学院 聊城 252059;
    3. 南开大学药学院 天津 300071
  • 收稿日期:2017-12-07 修回日期:2018-01-09 出版日期:2018-06-15 发布日期:2018-03-12
  • 通讯作者: 王庆鹏,e-mail:lywqp@126.com;李大成,e-mail:lidacheng62@163.com E-mail:lywqp@126.com;lidacheng62@163.com
  • 基金资助:
    山东省自然科学基金项目（No.ZR2017BH092，ZR2014HL105）、山东省抗体制药协同创新中心开放课题（No.CIC-AD1835，CIC-AD1836）、聊城大学博士基金项目（No.318051635）和山东省泰山学者研究基金项目资助
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Small Molecular Platinum(Ⅳ) Compounds as Antitumor Agents

Xiaoxiao Tan1,2, Guoshuai Li1, Qingpeng Wang1*, Bingquan Wang1, Dacheng Li1,2*, Peng George Wang3   

  1. 1. Institute of Biopharmaceutical Research, Liaocheng University, Liaocheng 252059, China;
    2. Department of Chemistry and Chemical Engineering, Liaocheng University, Liaocheng 252059, China;
    3. College of Pharmacy, Nankai University, Tianjin 300071, China
  • Received:2017-12-07 Revised:2018-01-09 Online:2018-06-15 Published:2018-03-12
  • Supported by:
    The work was supported by the Natural Science Foundation of Shandong (No.ZR2017BH092,ZR2014HL105),the Open Project of Shandong Collaborative Innovation Center for Antibody Drugs (No.CIC-AD1835,CIC-AD1836),the Doctoral Foundation of Liaocheng University (No.318051635),and the Taishan Scholar Research Foundation of Shandong.
四价铂类化合物作为抗肿瘤药物具有独特优势，显示出巨大的开发价值，受到广泛关注，近年来发展十分迅速，相关研究工作众多，已取得了许多杰出成果，是一个充满活力的热点领域。目前已有大量高活性、低毒性、耐药性低、生物利用率高、药代动力学性质优异、肿瘤靶向性强的四价铂化合物得到研究与开发，显示出了四价铂化合物在抗癌药物研究领域的巨大开发价值和深远的应用前景。目前对四价铂的开发主要集中在两方面：（1）基于经典铂类药物的四价铂，以二价铂药物为母体，通过引入不同功能的轴向配体，制备高活性多功能目标化合物。（2）基于非经典铂类药物的四价铂，对横向配体进行修饰制备新结构目标化合物，该类药物对于克服耐药性具有重要价值，特别是光敏四价铂有望为光动力学抗癌疗法提供新候选药物。四价铂具有发展为新一代可口服铂类药物的潜力。基于此，本文结合课题组在四价铂方面的工作基础，参考近五年本领域工作进展系统地综述了小分子四价铂化合物作为抗肿瘤药物的研究新进展，并对其发展趋势作了展望。
关键词： 铂类药物, 四价铂, 抗肿瘤, 前药, 多靶向药物
Platinum(Ⅳ) compounds which exert unique advantages as antitumor drugs,have aroused wide attention of researchers in pharmaceutical area. A great deal of efforts have been devoted to this field, and many remarkable results are achieved. The investigation on platinum(Ⅳ) compounds has become an active and hot topic. Large numbers of complexes with high activity, low toxicity, low drug-resistance, high bioavailability, satisfactory pharmacokinetic property and remarkable tumor targeting property have been prepared and evaluated in recent years. The current work is mainly focused on the following two aspects:(1) Platinum(Ⅳ) compounds based on classical platinum drugs. Various functional axial ligands are incorporated to platinum system to construct novel multi-functional platinum(Ⅳ) compounds with effective activities. (2) Platinum(Ⅳ) compounds based on non-classical platinum compounds are obtained by modifying the transverse ligands to prepare platinum(Ⅳ) complexes with non-classical platinum(Ⅱ) cores, and these target compounds have shown great competence in overcoming drug resistance of platinum drugs. Moreover, photosensitive platinum(Ⅳ) compounds have good performance in photodynamic therapy which is a new trend of clinical cancer treatment. Platinum(Ⅳ) compounds are of great potentials to be developed as the next generation of approved platinum anticancer drugs with oral administration. Herein, by combining authors' research and referring to the works from literatures in recent five years, the research progress of small molecular platinum(Ⅳ) compounds as antitumor agents is systematically reviewed, and the perspectives of the foreseeable future of platinum(Ⅳ) compounds as medicinal drugs are also presented.
Contents
1 Introduction
2 Platinum (Ⅳ) compounds based on classical platinum drugs
2.1 Lipid/water tuning
2.2 Membrane protein targeting
2.3 Energy metabolism enzyme targeting
2.4 Mitochondrial targeting
2.5 HSA targeting
2.6 Inflammatory factor targeting
2.7 DNA targeting
2.8 HDAC targeting
2.9 Others
3 Platinum (Ⅳ) compounds based on non-classical platinum compounds
3.1 Modification of stable ligands
3.2 Modification of leaving ligands
3.3 Photosensitive platinum (Ⅳ) compounds with azido ligands
4 Conclusion
Key words: platinum drug, platinum (Ⅳ), antitumor, prodrug, multi-targeting drug

中图分类号: 

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摘要

作为抗肿瘤药物的小分子四价铂