2. Academic Validation
  3. Synthesis and evaluation of novel podophyllotoxin derivatives as potential antitumor agents

Synthesis and evaluation of novel podophyllotoxin derivatives as potential antitumor agents

  • Eur J Med Chem. 2014 Oct 6:85:498-507. doi: 10.1016/j.ejmech.2014.08.006.
Wei-Hua Cheng 1,  Bo Cao 2,  Hai Shang 1,  Cong Niu 2,  Li-Ming Zhang 3,  Zhong-Heng Zhang 3,  Dan-Li Tian 4,  Shi Zhang 2,  Hong Chen 5,  Zhong-Mei Zou 6
Affiliations

Affiliations

  • 1 Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, PR China.
  • 2 Pharmacognosy Division, Medical College of Chinese People's Armed Police Force, Tianjin 300162, PR China.
  • 3 Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin 300070, PR China.
  • 4 Tianjin First Central Hospital, Tianjin 300192, PR China.
  • 5 Pharmacognosy Division, Medical College of Chinese People's Armed Police Force, Tianjin 300162, PR China; Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin 300070, PR China. Electronic address: chenhongtian06@163.com.
  • 6 Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, PR China. Electronic address: zmzou@implad.ac.cn.
PMID: 25113878 DOI: 10.1016/j.ejmech.2014.08.006
Abstract

Cancer multidrug resistance (MDR) is a common cause of treatment failure in Cancer patients. Increased expression of permeability glycoprotein (P-gp), which is also known as MDR-1, is the main cause of multidrug resistance. Podophyllotoxin derivatives hold great promise in the battle to overcome multidrug resistance, as they can induce cytotoxicity through multiple mechanisms. Here, we synthesized sixteen novel podophyllotoxin derivatives and evaluated their cytotoxicities in human Cancer cell lines, HeLa, K562 and K562/A02. Some of these compounds were more potent than etoposide, a clinically relevant inhibitor of DNA repair Enzymes. In particular, compound 5p exhibited the most potent activity toward drug-resistant K562/A02 cells, as it robustly inhibited tumor cell proliferation and induced Apoptosis. Furthermore, preliminary investigation suggested that 5p inhibited the expression of MDR-1 in K562/A02 cells more effectively than etoposide.

Keywords

Apoptosis; Cytotoxicity; MDR-1; Multidrug resistance; Podophyllotoxin.

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