Antitumor agents--CLI. Bis(helenalinyl)glutarate and bis(isoalantodiol-B)glutarate, potent inhibitors of human DNA topoisomerase II.
Evaluation of a number of cytotoxic antitumor sesquiterpene lactones and their derivatives has led to the discovery of bis(helenalinyl)glutarate (4) and bis(isoalantodiol-B)glutarate (10) as potent inhibitors of human-derived topoisomerase II. Unlike etoposide, which inhibits by preventing the DNA rejoining process, compounds 4 and 10 inhibit topoisomerase II without causing DNA breakage. The structure-activity relationships of 4, 10, and related compounds are discussed.
Chen
C H
CH
Natural Products Laboratory, Division of Medicinal Chemistry and Natural Products, School of Pharmacy, University of North Carolina, Chapel Hill 27599.
Yang
L M
LM
Lee
T T
TT
Shen
Y C
YC
Zhang
D C
DC
Pan
D J
DJ
McPhail
A T
AT
McPhail
D R
DR
Liu
S Y
SY
Li
D H
DH
D002460:Cell Line; D004247:DNA / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D006801:Humans; D066298:In Vitro Techniques; D007783:Lactones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D012717:Sesquiterpenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D059005:Topoisomerase II Inhibitors
D007783:Lactones; D012717:Sesquiterpenes; D059005:Topoisomerase II Inhibitors; C089679:bis(helenalinyl)glutarate; C089680:bis(isoalantodiol-B)glutarate; C089681:isoallantolactone epoxide; D004247:DNA