Abstract
Tumor blood vessels are an important emerging target for anti-cancer therapy. The antimitotic agent combretastatin A-4 (CA- 4), a cis-stilbene natural product isolated from the South African tree Combretum caffrum Kuntze, is the lead compound of a new class of anti-cancer drugs that target tumor vasculature. CA-4 inhibits tubulin polymerization by interacting at the colchicine binding site on tubulin. This alters the morphology of endothelial cells and causes vascular shutdown and regression of tumor vasculature.
Some tubulin-binding vascular-disrupting agents (VDAs) are currently in clinical trials for cancer therapy. As a consequence of the potential favorable applications of these compounds, several analogs projected to induce rapid and selective vascular shutdown in tumors have been synthesized during the last few years. Many of these molecules have already been tested for their effects on tubulin polymerization as well as for their antiproliferative activity and other biological properties, and possible mechanisms of action have been investigated.
The aim of the present review is to offer an overview of most recently developed combretastatin derivatives, focusing on biological effects exerted by these compounds. The published data about new analogs are presented and compared, and a detailed investigation of structure-activity relationships is described.
Keywords: Combretastatin A-4, combretastatin analogs, vascular disrupting agents, tubulin, structure-activity relationships, Tumor blood vessels, anti-cancer therapy, cis-stilbene, Combretum caffrum Kuntze, VDAs
Current Medicinal Chemistry
Title: Biological Potential and Structure-Activity Relationships of Most Recently Developed Vascular Disrupting Agents: An Overview of New Derivatives of Natural Combretastatin A-4
Volume: 18 Issue: 20
Author(s): M. Marrelli, F. Conforti, G. A. Statti, X. Cachet, S. Michel, F. Tillequin and F. Menichini
Affiliation:
Keywords: Combretastatin A-4, combretastatin analogs, vascular disrupting agents, tubulin, structure-activity relationships, Tumor blood vessels, anti-cancer therapy, cis-stilbene, Combretum caffrum Kuntze, VDAs
Abstract: Tumor blood vessels are an important emerging target for anti-cancer therapy. The antimitotic agent combretastatin A-4 (CA- 4), a cis-stilbene natural product isolated from the South African tree Combretum caffrum Kuntze, is the lead compound of a new class of anti-cancer drugs that target tumor vasculature. CA-4 inhibits tubulin polymerization by interacting at the colchicine binding site on tubulin. This alters the morphology of endothelial cells and causes vascular shutdown and regression of tumor vasculature.
Some tubulin-binding vascular-disrupting agents (VDAs) are currently in clinical trials for cancer therapy. As a consequence of the potential favorable applications of these compounds, several analogs projected to induce rapid and selective vascular shutdown in tumors have been synthesized during the last few years. Many of these molecules have already been tested for their effects on tubulin polymerization as well as for their antiproliferative activity and other biological properties, and possible mechanisms of action have been investigated.
The aim of the present review is to offer an overview of most recently developed combretastatin derivatives, focusing on biological effects exerted by these compounds. The published data about new analogs are presented and compared, and a detailed investigation of structure-activity relationships is described.
Export Options
About this article
Cite this article as:
Marrelli M., Conforti F., A. Statti G., Cachet X., Michel S., Tillequin F. and Menichini F., Biological Potential and Structure-Activity Relationships of Most Recently Developed Vascular Disrupting Agents: An Overview of New Derivatives of Natural Combretastatin A-4, Current Medicinal Chemistry 2011; 18 (20) . https://dx.doi.org/10.2174/092986711796391642
DOI https://dx.doi.org/10.2174/092986711796391642 |
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
-
miRNA and Proteomic Dysregulation in Non-Small Cell Lung Cancer in Response to Cigarette Smoke
MicroRNA Drug Metabolite Generation Using a Laboratory Evolved NADPH Independent Cytochrome P450: Application of in vitro and in silico Approaches
Drug Metabolism Letters Safety Profiles and Pharmacovigilance Considerations for Recently Patented Anticancer Drugs: Cutaneous Melanoma
Recent Patents on Anti-Cancer Drug Discovery Lymphatics and Inflammation
Current Medicinal Chemistry Pharmaceutical Applications of Graphene-based Nanosheets
Current Pharmaceutical Biotechnology Protease-Activated Receptor 2: Are Common Functions in Glial and Immune Cells Linked to Inflammation-Related CNS Disorders?
Current Drug Targets Radioimmunotherapy of Cancer Using Monoclonal Antibodies to Target Radiotherapy
Current Pharmaceutical Design DNA Demethylating Agents and Chromatin-Remodelling Drugs: Which, How and Why?
Current Drug Metabolism The Therapeutic Target Hsp90 and Cancer Hallmarks
Current Pharmaceutical Design A Glucuronic Acid Binding Leguminous Lectin with Mitogenic Activity Toward Mouse Splenocytes
Protein & Peptide Letters Recent Advances in Multinuclear Complexes as Potential Anticancer and DNA Binding Agents
Anti-Cancer Agents in Medicinal Chemistry Identification of New Targets for Therapy of Osteolytic Bone Disease in Multiple Myeloma
Current Drug Targets Anticancer Therapeutic Strategies Based on CDK Inhibitors
Current Pharmaceutical Design Purine Nucleoside Analogues for the Treatment of Hematological Malignancies: Pharmacology and Clinical Applications
Current Cancer Drug Targets Evaluation of Pregabalin Therapy in Peripheral Neuropathy
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Radiotracers for Molecular Imaging of Cyclooxygenase-2 (COX-2) Enzyme
Current Medicinal Chemistry Pharmacogenetics, Regulation and Structural Properties of the Drugmetabolizing Enzymes Arylamine N-acetyltransferases
Current Pharmacogenomics The CLCA Gene Family: Putative Therapeutic Target for Respiratory Diseases
Inflammation & Allergy - Drug Targets (Discontinued) Aptamers as Innovative Diagnostic and Therapeutic Agents in the Central Nervous System
CNS & Neurological Disorders - Drug Targets Large-Scale and Facile Synthesis of Biocompatible Yb-Based Nanoparticles as a Contrast Agent for In Vivo X-Ray Computed Tomography Imaging
Current Topics in Medicinal Chemistry