Antitumor agents. 123. Synthesis and human DNA topoisomerase II inhibitory activity of 2'-chloro derivatives of etoposide and 4 beta-(arylamino)-4'-O-demethylpodophyllotoxins

  • J Med Chem. 1992 Mar 6;35(5):866-71. doi: 10.1021/jm00083a009.
H Hu  1 ,  Z Q Wang ,  S Y Liu ,  Y C Cheng ,  K H Lee
Affiliations
  • 1. Natural Products Laboratory, School of Pharmacy, University of North Carolina, Chapel Hill 27599.
PMID: 1312600 DOI: 10.1021/jm00083a009
Abstract

The 2'-chloro derivatives of etoposide and 4 beta-(arylamino)-4'-O-demethylpodophyllotoxins have been synthesized and evaluated for their inhibitory activity against the human DNA Topoisomerase II as well as for their activity in causing cellular protein-linked DNA breakage. The results showed that none of the compounds are active as a result of the C-2' chloro substitution on ring E. This would suggest that the free rotation of ring E is essential for the aforementioned enzyme inhibitory activity. In addition, these 2'-chloro derivatives showed no significant cytotoxicity (KB).