First synthesis and biological evaluation of novel spin-labeled derivatives of deoxypodophyllotoxin

Eur J Med Chem. 2010 Apr;45(4):1673-7. doi: 10.1016/j.ejmech.2009.12.032. Epub 2009 Dec 23.

Abstract

Deoxypodophyllotoxin inhibits tubulin polymerization and induces cell cycle arrest at G2/M, followed by apoptosis. In order to find compounds with superior bioactivity and less toxicity, a series of spin-labeled derivatives of deoxypodophyllotoxin were synthesized by reacting 4'-demethyl-4-deoxypodophyllotoxin (DPPT) with N-(1-oxyl-2,2,6,6-tetramethyl-4-piperidinyloxycarbonyl) amino acids. The cytotoxic activities against three tumor cell lines (HL-60, RPMI-8226, A-549) in vitro and the antioxidative activities in tissues of Sprague Dawley (SD) rats of target compounds were evaluated, and the results indicated that compounds 11a-h were more potent in terms of cytotoxicities and antioxidative activities than either parent compound DPPT or anticancer drug VP-16.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / chemical synthesis*
  • Antioxidants / chemistry
  • Antioxidants / pharmacology*
  • Cell Line
  • Drugs, Chinese Herbal
  • Humans
  • Podophyllotoxin / analogs & derivatives*
  • Podophyllotoxin / chemical synthesis
  • Podophyllotoxin / chemistry
  • Podophyllotoxin / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Spectrometry, Mass, Electrospray Ionization
  • Spectrophotometry, Infrared
  • Spin Labels

Substances

  • Antioxidants
  • Drugs, Chinese Herbal
  • Spin Labels
  • deoxypodophyllotoxin
  • Podophyllotoxin