Antitumor agents. 123. Synthesis and human DNA topoisomerase II inhibitory activity of 2'-chloro derivatives of etoposide and 4 beta-(arylamino)-4'-O-demethylpodophyllotoxins.
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).
Hu
H
H
Natural Products Laboratory, School of Pharmacy, University of North Carolina, Chapel Hill 27599.
Wang
Z Q
ZQ
Liu
S Y
SY
Cheng
Y C
YC
Lee
K H
KH
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004249:DNA Damage; D005047:Etoposide / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D007624:KB Cells / Q000187:drug effects; D015394:Molecular Structure; D011034:Podophyllotoxin / Q000031:analogs & derivatives*; D013329:Structure-Activity Relationship; D013388:Succinimides / Q000737:chemistry; D059005:Topoisomerase II Inhibitors
D000970:Antineoplastic Agents; D013388:Succinimides; D059005:Topoisomerase II Inhibitors; C015752:N-chlorosuccinimide; C073520:2'-chloroetoposide; D005047:Etoposide; D011034:Podophyllotoxin