2. Academic Validation
  3. A series of camptothecin prodrugs exhibit HDAC inhibition activity

A series of camptothecin prodrugs exhibit HDAC inhibition activity

  • Bioorg Med Chem. 2018 Sep 1;26(16):4706-4715. doi: 10.1016/j.bmc.2018.08.008.
Qiwen Zhu 1,  Xumeng Yu 1,  Qianqian Shen 2,  Qiumeng Zhang 3,  Mingbo Su 4,  Yubo Zhou 4,  Jia Li 4,  Yi Chen 5,  Wei Lu 6
Affiliations

Affiliations

  • 1 Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, 3663 North Zhongshan Road, Shanghai 200062, PR China.
  • 2 Division of Anti-Tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR China.
  • 3 Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, 3663 North Zhongshan Road, Shanghai 200062, PR China; National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR China.
  • 4 National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR China.
  • 5 Division of Anti-Tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR China. Electronic address: ychen@simm.ac.cn.
  • 6 Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, 3663 North Zhongshan Road, Shanghai 200062, PR China. Electronic address: wlu@chem.ecnu.edu.cn.
PMID: 30115492 DOI: 10.1016/j.bmc.2018.08.008
Abstract

Camptothecin plays an important role in clinical Cancer treatment, and its derivatives are a favorite of pharmaceutical chemists. Herein, we have designed a series of camptothecin prodrugs that exhibit histone deacetylase (HDAC) inhibition activity based on the synergy effect between HDAC inhibitors and camptothecin derivatives. With the evaluation of stability in buffers or plasma from human or mouse model, an appropriate linker was found, so the active drug can be released efficiently and compound 21a exhibited strong antiproliferative activity in A549 and HCT-116 cell lines. These results indicated that the well-designed prodrug can be promising in Cancer treatment.

Keywords

Camptothecin; HDAC; Prodrug; SAHA.

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