Nitro and amino substitution within the A-ring of 5H-8,9-dimethoxy-5-(2-N, N-dimethylaminoethyl)dibenzo[c,h][1,6]naphthyridin-6-ones: Influence on topoisomerase I-targeting activity and cytotoxicity
Journal
Bioorganic and Medicinal Chemistry
Journal Volume
12
Journal Issue
13
Pages
3731-3742
Date Issued
2004
Author(s)
Abstract
Recently, 5H-8,9-dimethoxy-5-(2-N,N-dimethylaminoethyl)-2,3- methylenedioxydibenzo[c,h][1,6]naphthyridin-6-one, 1, was identified as a TOP1-targeting agent with pronounced antitumor activity. In the present study, the effect on activity of substituting a single nitro or amino group in the A-ring in lieu of the methylenedioxy moiety of 1 was evaluated. The presence of either a nitro or amino substituent at the 4-position had a pronounced adverse affect on both TOP1-targeting activity and cytotoxicity. To a lesser extent, derivatives with a nitro or amino substituent at the 1-position were also less active than 1. Replacement of the methylenedioxy moiety of 1 with either a nitro or amino substituent at either the 2- and 3-position did result in analogues with potent TOP1-targeting activity and cytotoxicity. © 2004 Elsevier Ltd. All rights reserved.
SDGs
Type
journal article