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

1998-05-05

Jordan, Charles T.

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Having -c-, wherein x is chalcogen, bonded directly to...

548421, 549298, A01N 4338, C07D48700, C07D30777

Patent

active

057475202

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 quasi-planar 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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