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Updated: Aug 21, 2026

Simple and Fast Rolling Circle Amplification-Based Detection of Topoisomerase 1 Activity in Crude Biological Samples
Published on: December 2, 2022
AK37: the first pyridoacridine described capable of stabilizing the topoisomerase I cleavable complex
Kathryn M Marshall1, Joseph A Holden, Avi Koller
1Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, UT 84112, USA.
Abstract:
Pyridoacridines are marine natural products that contain planar structures. Almost all are cytotoxic and capable of DNA intercalation. Several pyridoacridines have demonstrated anti-cancer activity, being able to generate reactive oxygen species or to inhibit topoisomerase (Topo) II. Synthetic pyridoacridines were characterized and compared to other pyridoacridines as well as the Topo-inhibiting drugs (etoposide, 9-aminocamptothecin and wakayin) in a series of in vitro enzyme systems. We found AK37 was able to stabilize a DNA-Topo I cleavable complex, but not a DNA-Topo II cleavable complex. To our knowledge, this is the first report of a DNA-Topo I cleavable complex stabilizing pyridoacridine. Structure comparison studies demonstrated that this activity was lost when an extra 'F' ring was added, but activity was not affected when the 'D' ring was removed. AK37 inhibited the catalytic activity of both human Topo I and II.
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