Antitumor Agents 126. Novel 4β-Substituted Anilino Derivatives of 3′,4′ - O, O-Didemethylpodophyllotoxin as Potent Inhibitors of Human DNA Topoisomerase II

Zhe Qing Wang, Ya Ching Shen, Hong Xing Chen, Jang Yang Chang, Xin Guo, Yung Chi Cheng, Kuo Hsiung Lee

研究成果: Article

13 引文 斯高帕斯(Scopus)

摘要

A series of derivatives of 3′,4′ 0,0-didemethylpodophyllotoxin have been synthesized and evaluated for their inhibitor activity against neoplastic cell growth (KB) and against human DNA topoisomerase II as well as for their activity in causing cellular protein-linked DNA breakage. The results show that the compounds possessing a 4β-anilino moiety either unsubstituted or substituted at the para (F, COOCH3, COCH3, CN, CH2CN, NO2) or meta (OH) positions or with an ethylenedioxy moiety showed the same or greater activity than etoposide in causing cellular protein-linked DNA breakage and in inhibiting DNA topoisomerase II. However, compared to the corresponding 4′- 0-demethyl analogues, the 3′,4′- O,O-didemethyl compounds have a similar potency in inhibition of DNA topoisomerase II but are less active in causing cellular protein-linked DNA breakage. Complete correlation between the three biological activities–cytotoxicity, inhibition of DNA topoisomerase II, and induction of protein-linked DNA breakage–was also not observed. This supports the possibility that the biological determinants of action among these compounds may be different.

原文English
頁(從 - 到)343-350
頁數8
期刊Pharmaceutical Research: An Official Journal of the American Association of Pharmaceutical Scientists
10
發行號3
DOIs
出版狀態Published - 1993 三月

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)

指紋 深入研究「Antitumor Agents 126. Novel 4β-Substituted Anilino Derivatives of 3′,4′ - O, O-Didemethylpodophyllotoxin as Potent Inhibitors of Human DNA Topoisomerase II」主題。共同形成了獨特的指紋。

  • 引用此