Diaza- and triazachrysenes: Potent topoisomerase-targeting agents with exceptional antitumor activity against the human tumor xenograft, MDA-MB-435
Journal
Bioorganic and Medicinal Chemistry Letters
Journal Volume
12
Journal Issue
22
Pages
3333-3336
Date Issued
2002
Author(s)
Abstract
Several 5,12-diazachrysen-6-ones and 5,6,11-triazachrysen-12-ones were synthesized with varied substituents at the 5- or 11-position, respectively. Each compound was evaluated for its potential to stabilize the cleavable complex formed with TOP1 and DNA. Two analogues with very potent TOP1-targeting activity, 3a and 4a, exhibited cytotoxic activity with IC(50) values at or below 2nM against RPMI8402. Compound 3a was active in vivo by either ip or po administration in the human tumor xenograft athymic nude mice model.
SDGs
Type
journal article