Antitumor Agents. 120. New 4-Substituted Benzylamine and Benzyl Ether Derivatives of 4′-O-Demethylepipodophyollotoxin as Potent Inhibitors of Human DNA Topoisomerase II

Xiao Ming Zhou, Zhe Qing Wang, Kuo Hsiung Lee, Jang Yang Chang, Hong Xing Chen, Yung Chi Cheng

Research output: Contribution to journalArticlepeer-review

68 Citations (Scopus)

Abstract

A number of new 4′-O-demethylepipodophyllotoxin derivatives possessing various 4β-N- or 4β-O-benzyl groups 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 4β-N-benzyl derivatives 9-22 are, in general, as active or more active than etoposide (1). The most active compounds are 14,16, and 17, which are more than 2-fold more potent than 1. The results indicated that a basic unsubstituted 4β-benzylamino moiety is structurally required for the enhanced activity. Replacement of the benzyl nitrogen with oxygen gave compounds (23 and 24) which are inactive. The ability of these compounds to inhibit human DNA topoisomerase II and to cause protein-linked DNA breakage appears to have no direct correlation with cytotoxicity in KB cells.

Original languageEnglish
Pages (from-to)3346-3350
Number of pages5
JournalJournal of Medicinal Chemistry
Volume34
Issue number12
DOIs
Publication statusPublished - 1991 Dec 1

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Drug Discovery

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