Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET

User menu

  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
Molecular Pharmacology
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET
  • My alerts
  • Log in
  • My Cart
Molecular Pharmacology

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Visit molpharm on Facebook
  • Follow molpharm on Twitter
  • Follow molpharm on LinkedIn
Abstract

Inhibition of DNA topoisomerase II by imidazoacridinones, new antineoplastic agents with strong activity against solid tumors.

A Skladanowski, S Y Plisov, J Konopa and A K Larsen
Molecular Pharmacology May 1996, 49 (5) 772-780;
A Skladanowski
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
S Y Plisov
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
J Konopa
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
A K Larsen
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Info & Metrics
  • eLetters
  • PDF
Loading

Abstract

Imidazoacridinones are new antitumor compounds that exhibit strong antitumor effect against solid tumors such as human colon and breast carcinomas. The mechanism of action of imidazoacridinones is unknown, although a similarity in the chemical structure between active imidazoacridinones and mitoxantrone suggests common cellular targets. We show that imidazoacridinones inhibit the catalytic activity of purified topoisomerase II as determined by both relaxation and decatenation assays. All biologically active compounds stimulated the formation of cleavable complexes in vitro, whereas inactive compounds did not. The pattern of DNA cleavage in SV40 DNA was similar to that obtained for 4'-(9-acridinylamino)methane-sulfon-m-aniside, particularly within the matrix-associated region. Significant levels of DNA complexes were observed when DC-3F fibrosarcoma cells were treated with active compounds, whereas negligible amounts of these complexes were induced by inactive analogues. DC-3F/9-OHE cells, which are resistant to other topoisomerase II inhibitors, are 30-125-fold cross-resistant to active imidazoacridinones. The resistance is associated with a reduction in the formation of DNA/protein complexes and is highest for compounds that are potent topoisomerase II inhibitors in vitro. Interestingly, the two most active derivatives, C-1310 and C-1311, were equally cytotoxic toward fast-growing monolayer cultures and cells growing in three dimensions as multicellular spheroids, which have a slower growth fraction. In contrast, 4'-(9-acridinylamino)methanesulfon-m-aniside, mitoxantrone, and doxorubicin were more cytotoxic toward monolayer cultures. Taken together, the results suggest that DNA topoisomerase II is a major cellular target of biologically active imidazoacridinones and that these drugs show both similarities and dissimilarities compared with classic topoisomerase II inhibitors.

MolPharm articles become freely available 12 months after publication, and remain freely available for 5 years. 

Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page. 

 

  • Click here for information on institutional subscriptions.
  • Click here for information on individual ASPET membership.

 

Log in using your username and password

Forgot your user name or password?

Purchase access

You may purchase access to this article. This will require you to create an account if you don't already have one.
PreviousNext
Back to top

In this issue

Molecular Pharmacology
Vol. 49, Issue 5
1 May 1996
  • Table of Contents
  • Table of Contents (PDF)
  • Index by author
  • Back Matter (PDF)
  • Editorial Board (PDF)
  • Front Matter (PDF)
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Molecular Pharmacology article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Inhibition of DNA topoisomerase II by imidazoacridinones, new antineoplastic agents with strong activity against solid tumors.
(Your Name) has forwarded a page to you from Molecular Pharmacology
(Your Name) thought you would be interested in this article in Molecular Pharmacology.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Abstract

Inhibition of DNA topoisomerase II by imidazoacridinones, new antineoplastic agents with strong activity against solid tumors.

A Skladanowski, S Y Plisov, J Konopa and A K Larsen
Molecular Pharmacology May 1, 1996, 49 (5) 772-780;

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero

Share
Abstract

Inhibition of DNA topoisomerase II by imidazoacridinones, new antineoplastic agents with strong activity against solid tumors.

A Skladanowski, S Y Plisov, J Konopa and A K Larsen
Molecular Pharmacology May 1, 1996, 49 (5) 772-780;
Reddit logo Twitter logo Facebook logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

Similar Articles

Advertisement
  • Home
  • Alerts
Facebook   Twitter   LinkedIn   RSS

Navigate

  • Current Issue
  • Fast Forward by date
  • Fast Forward by section
  • Latest Articles
  • Archive
  • Search for Articles
  • Feedback
  • ASPET

More Information

  • About Molecular Pharmacology
  • Editorial Board
  • Instructions to Authors
  • Submit a Manuscript
  • Customized Alerts
  • RSS Feeds
  • Subscriptions
  • Permissions
  • Terms & Conditions of Use

ASPET's Other Journals

  • Drug Metabolism and Disposition
  • Journal of Pharmacology and Experimental Therapeutics
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-0111 (Online)

Copyright © 2023 by the American Society for Pharmacology and Experimental Therapeutics