Synthesis and biological evaluation of tetrademethyl isocolchicine derivatives as inhibitors of DNA topoisomerase action in vitro.
Four tetrademethyl isocolchicine analogs were prepared and evaluated as inhibitors of mammalian DNA topoisomerase in vitro. All compounds inhibited topoisomerase II-dependent DNA unknotting by a mechanism which did not involve "cleavable-complex" formation. N-Deacetylation as well as N-substitution with the (3',4',5'-trihydroxybenzoyl)-group afforded compounds which were less selective, based on their added ability to inhibit topoisomerase I-mediated DNA relaxation.
Bastow
K F
KF
Division of Medicinal Chemistry and Natural Products, School of Pharmacy, University of North Carolina, Chapel Hill 27599.
Tatematsu
H
H
Sun
L
L
Fukushima
Y
Y
Lee
K H
KH
D003078:Colchicine / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D006367:HeLa Cells; D006801:Humans; D066298:In Vitro Techniques; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors
D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; C059352:isocolchicine; D004247:DNA; D003078:Colchicine