Abstract
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.
Current Medicinal Chemistry
Title: Recent Developments of Rebeccamycin Analogues as Topoisomerase I Inhibitors and Antitumor Agents.
Volume: 7 Issue: 12
Author(s): Michelle Prudhomme
Affiliation:
Abstract: 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.
Export Options
About this article
Cite this article as:
Prudhomme Michelle, Recent Developments of Rebeccamycin Analogues as Topoisomerase I Inhibitors and Antitumor Agents., Current Medicinal Chemistry 2000; 7 (12) . https://dx.doi.org/10.2174/0929867003374138
DOI https://dx.doi.org/10.2174/0929867003374138 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Visceral Adipose Tissue and Atherosclerosis
Current Vascular Pharmacology Reversing Agents for ATP-Binding Cassette (ABC) Transporters: Application in Modulating Multidrug Resistance (MDR)
Current Medicinal Chemistry - Anti-Cancer Agents Current Developments of Coumarin Compounds in Medicinal Chemistry
Current Pharmaceutical Design ICH Q8 Guidelines in Practice: Spray Drying Process Optimization by 2<sup>3</sup> Factorial Design for the Production of Famotidine Nanoparticles
Pharmaceutical Nanotechnology Growth-hormone-releasing Hormone as a Prognostic Biomarker and Therapeutic Target in Gastrointestinal Cancer
Current Cancer Drug Targets Editorial [Hot Topic: Molecular Targeted Therapy of Gastrointestinal Cancer (Guest Editor: Marcus W. Wiedmann)]
Current Cancer Drug Targets Anticancer Effects of Garlic and Garlic-derived Compounds for Breast Cancer Control
Anti-Cancer Agents in Medicinal Chemistry Gold(III) Complexes in the Oncological Preclinical Arena: From Aminoderivatives to Peptidomimetics
Current Topics in Medicinal Chemistry Neurotoxins: Free Radical Mechanisms and Melatonin Protection
Current Neuropharmacology Anti-Diabetic Compounds and their Patent Information: An Update
Recent Patents on Inflammation & Allergy Drug Discovery Recent Progress in Phosphoinositide 3-Kinases: Oncogenic Properties and Prognostic and Therapeutic Implications
Current Protein & Peptide Science Novel Intervention Strategies for Helicobacter pylori Treatment
Current Drug Targets - Infectious Disorders Ribosomal Proteins and Colorectal Cancer
Current Genomics MicroRNA: Biogenesis, Function and Role in Cancer
Current Genomics Defining and Managing Expectations for Early Immunotherapy Cancer Trials
Reviews on Recent Clinical Trials From Nanotechnology to Nanomedicine: Applications to Cancer Research
Current Molecular Medicine Synthesis and In Vitro Enzymatic Studies of New 3-Aryldiazenyl Indoles as Promising Helicobacter pylori IMPDH Inhibitors
Current Topics in Medicinal Chemistry Role of Tyrosine Phosphatase Inhibitors in Cancer Treatment with Emphasis on SH2 Domain-Containing Tyrosine Phosphatases (SHPs)
Anti-Cancer Agents in Medicinal Chemistry Evolutionary Significance of Iodine
Current Chemical Biology From NAFLD to NASH and HCC: Pathogenetic Mechanisms and Therapeutic Insights
Current Pharmaceutical Design