Abstract
DNA topoisomerase I is required for DNA relaxation during a variety of cellular functions. The identification of camptothecins as specific enzyme poisons and their clinical efficacy have stimulated extensive efforts to exploit topoisomerase I as a therapeutic target for cancer. However, several limitations of camptothecins, such as low solubility and stability, high toxicity, and the occurrence of resistance, have encouraged the development of non-camptothecin topoisomerase I inhibitors. Different natural and synthetic compounds (e.g., indolocarbazoles, dibenzonaphthyridine and indenoisoquinoline) have been extensively studied as alternatives to camptothecins and have been proved to be promising therapeutic agents. In this review, we comparatively evaluate the preclinical results obtained with the different non-camptothecin poisons proposed thus far as topoisomerase I inhibitors, with special reference to cellular pharmacology, and discuss the perspective for their use in the clinical setting.
Keywords: Cellular pharmacology, Clinical studies, Dibenzonaphthyridines, DNA topoisomerase I, Drug resistance, Indenoisoquinolines, Indolocarbazoles, Lamellarins, Topopyrones, Tumor cells
Current Medicinal Chemistry
Title: Targeting DNA Topoisomerase I with Non-Camptothecin Poisons
Volume: 19 Issue: 8
Author(s): G. L. Beretta, V. Zuco, P. Perego and N. Zaffaroni
Affiliation:
Keywords: Cellular pharmacology, Clinical studies, Dibenzonaphthyridines, DNA topoisomerase I, Drug resistance, Indenoisoquinolines, Indolocarbazoles, Lamellarins, Topopyrones, Tumor cells
Abstract: DNA topoisomerase I is required for DNA relaxation during a variety of cellular functions. The identification of camptothecins as specific enzyme poisons and their clinical efficacy have stimulated extensive efforts to exploit topoisomerase I as a therapeutic target for cancer. However, several limitations of camptothecins, such as low solubility and stability, high toxicity, and the occurrence of resistance, have encouraged the development of non-camptothecin topoisomerase I inhibitors. Different natural and synthetic compounds (e.g., indolocarbazoles, dibenzonaphthyridine and indenoisoquinoline) have been extensively studied as alternatives to camptothecins and have been proved to be promising therapeutic agents. In this review, we comparatively evaluate the preclinical results obtained with the different non-camptothecin poisons proposed thus far as topoisomerase I inhibitors, with special reference to cellular pharmacology, and discuss the perspective for their use in the clinical setting.
Export Options
About this article
Cite this article as:
L. Beretta G., Zuco V., Perego P. and Zaffaroni N., Targeting DNA Topoisomerase I with Non-Camptothecin Poisons, Current Medicinal Chemistry 2012; 19 (8) . https://dx.doi.org/10.2174/092986712799320529
DOI https://dx.doi.org/10.2174/092986712799320529 |
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
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
Current advances in inherited cardiomyopathy
Describe in detail all novel advances in multimodality imaging related to inherited cardiomyopathy diagnosis and prognosis. Shed light to deeper phenotypic characterization. Acknowledge recent advances in genetics, genomics and precision medicineread 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
-
COX-2 and Colorectal Cancer
Current Pharmaceutical Design Obesity and Asthma
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Flavones as a Privileged Scaffold in Drug Discovery: Current Developments
Current Organic Synthesis Modulation of Energy Intake and Expenditure Due to Habitual Physical Exercise
Current Pharmaceutical Design DNA Repair Inhibitors: The Next Major Step to Improve Cancer Therapy
Current Topics in Medicinal Chemistry Advanced Neoplastic Disease as Immunologic, Endocrine and Metabolic Disorder
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Cancer Prevention and Therapy in a Preclinical Mouse Model: Impact of FHIT Viruses
Current Gene Therapy Antioxidant Activity of Galantamine and Some of its Derivatives
Current Medicinal Chemistry Recent Advances in Protein and Peptide Drug Delivery: A Special Emphasis on Polymeric Nanoparticles
Protein & Peptide Letters The Production of Solid Dosage Forms from Non-Degradable Polymers
Current Pharmaceutical Design Portal Vein Embolization: A Preoperative Approach to Improve the Safety of Major Hepatic Resection
Current Medical Imaging Recent Patents on Oral Insulin Delivery
Recent Patents on Drug Delivery & Formulation Green Approaches for Cancers Management: An Effective Tool for Health Care
Anti-Cancer Agents in Medicinal Chemistry Targeting MDM2-p53 Interaction for Cancer Therapy: Are We There Yet?
Current Medicinal Chemistry Cardiac Imaging in Heart Failure with Comorbidities
Current Cardiology Reviews The High Mobility Group A1 (HMGA1) Transcriptome in Cancer and Development
Current Molecular Medicine Intracellular ROS Generation Mediates Maleimide-induced Cytotoxicity in Leukemia Cells
Anti-Cancer Agents in Medicinal Chemistry Beta-glucans is a Potential Inhibitor of Ovarian Cancer: Based on Molecular and Biological Aspects
Current Pharmaceutical Biotechnology Small-Animal Molecular Imaging for Preclinical Cancer Research: μPET and μSPECT
Current Radiopharmaceuticals Decreasing the Metastatic Potential in Cancers - Targeting the Heparan Sulfate Proteoglycans
Current Drug Targets