Generic placeholder image

Current Medicinal Chemistry


ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Recent Developments of Rebeccamycin Analogues as Topoisomerase I Inhibitors and Antitumor Agents.

Author(s): Michelle Prudhomme

Volume 7, Issue 12, 2000

Page: [1189 - 1212] Pages: 24

DOI: 10.2174/0929867003374138

Price: $65


DNA topoisomerases are essential for the survival of prokaryotic and eukaryotic organisms. Topoisomerases inhibitors, due to their capacity to induce DNA breaking, can exhibit interesting antitumor properties. While there are many potent antitumor agents which target topoisomerase II, relatively few families of specific topoisomerase I inhibitors have been identified. The present review describes a new family of topoisomerase I inhibitors, analogues of the bacterial metabolite rebeccamycin. These compounds possess an indolocarbazole chromophore onto which is attached a sugar residue. Important structure-activity relationships studies in this series have helped to understand the role of the carbohydrate moiety which is absolutely necessary for topoisomerase I poisoning, the influence of the stereochemistry (α or β) of its linkage to indole, the influence of the functionalities and substitutions on the sugar moiety and on the aromatic framework have been investigated. In addition to their action on DNA, rebeccamycin analogues may inhibit the SR kinase activity of topoisomerase I and therefore constitute a unique family of topoisomerase I poisons quite different from the well known camptothecins.

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy