Topoisomerase II inhibitors and therapeutic uses therefor

Details Topoisomerase II inhibitors and therapeutic uses therefor Topoisomerase II inhibitors and therapeutic uses therefor

1995-06-02

1997-02-25

Mai, Ngoclan

Organic compounds -- part of the class 532-570 series

Organic compounds

Heterocyclic carbon compounds containing a hetero ring...

546 86, 546 89, C07D47100

Patent

active

056060602

ABSTRACT:
Azatoxin and derivatives thereof are illustrative of a new class of antitumor drugs that are topoisomerase II (top 2) inhibitors. The pharmacophore inhibits the catalytic activity of the purified enzyme but does not unwind relaxed or supercoiled DNA. It is nonintercalative and has at least two domains: a quasiplanar polycyclic ring system, which may bind between DNA base pairs, and a pendant substituent thought to interact with the enzyme, with the DNA grooves or with both. In SV40 and c-myc DNA, azatoxin induces numerous double-strand breaks according to a cleavage pattern which differs from those of known top 2 inhibitors. Azatoxin also is a potent inhibitor of tubulin polymerization.

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