Abstract
Combretastatin A-4 (CA-4) is a natural product, which consists of two phenyl rings, linked by an ethylene bridge. CA-4, inhibitor of polymerization of tubulin to microtubules, possesses a strong antitumor and anti-vascular properties both in vitro and in vivo. Previous studies showed that disodium phosphate salt of CA-4, a water-soluble prodrug is well tolerated at therapeutically useful doses. However, it should be noted that the cis-configuration of the double bond and the 3,4,5-trimethoxy group on ring A is necessary for the biological activity of CA-4. Structure of CA-4 renders the compound readily susceptible to isomerization, which reduces the potency and bioavailability. To circumvent this problem, a lot of scientists in the world synthesized a series of cis-restricted CA-4 analogs, where the double bond has been replaced by introduction of non-heterocyclic groups or heterocyclic groups like β -lactam and oxadiazole. This paper reviews the most important approaches in analogs of combretastatin synthesis and presents structure-reactivity relationships for these compounds.
Keywords: Combretastatin A-4, CA-4, Inhibitors of angiogenesis, Synthesis; Biological activity, Cancer therapy.
Anti-Cancer Agents in Medicinal Chemistry
Title:Synthesis of Combretastatin A-4 Analogs and their Biological Activities
Volume: 16 Issue: 8
Author(s): Agnieszka Siebert, Monika Gensicka, Grzegorz Cholewinski and Krystyna Dzierzbicka
Affiliation:
Keywords: Combretastatin A-4, CA-4, Inhibitors of angiogenesis, Synthesis; Biological activity, Cancer therapy.
Abstract: Combretastatin A-4 (CA-4) is a natural product, which consists of two phenyl rings, linked by an ethylene bridge. CA-4, inhibitor of polymerization of tubulin to microtubules, possesses a strong antitumor and anti-vascular properties both in vitro and in vivo. Previous studies showed that disodium phosphate salt of CA-4, a water-soluble prodrug is well tolerated at therapeutically useful doses. However, it should be noted that the cis-configuration of the double bond and the 3,4,5-trimethoxy group on ring A is necessary for the biological activity of CA-4. Structure of CA-4 renders the compound readily susceptible to isomerization, which reduces the potency and bioavailability. To circumvent this problem, a lot of scientists in the world synthesized a series of cis-restricted CA-4 analogs, where the double bond has been replaced by introduction of non-heterocyclic groups or heterocyclic groups like β -lactam and oxadiazole. This paper reviews the most important approaches in analogs of combretastatin synthesis and presents structure-reactivity relationships for these compounds.
Export Options
About this article
Cite this article as:
Siebert Agnieszka, Gensicka Monika, Cholewinski Grzegorz and Dzierzbicka Krystyna, Synthesis of Combretastatin A-4 Analogs and their Biological Activities, Anti-Cancer Agents in Medicinal Chemistry 2016; 16 (8) . https://dx.doi.org/10.2174/1871520616666160204111832
DOI https://dx.doi.org/10.2174/1871520616666160204111832 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
- 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
Related Articles
-
Novel Approaches for Modulating dUTPase and Uracil-DNA Glycosylase: Potential Uses for Cancer and Viral Chemotherapy
Drug Design Reviews - Online (Discontinued) Normal Cytochrome c Oxidase Activity in Prion Protein Gene-Deficient Mice
Protein & Peptide Letters Hepatocyte Growth Factor and Insulin-like Growth Factor-1 based Cellular Therapies for Oxidative Stress Injury
Current Stem Cell Research & Therapy Multiple Defects in Energy Metabolism in Alzheimers Disease
Current Drug Targets Oncogenic Fusion Tyrosine Kinases as Molecular Targets for Anti-Cancer Therapy
Anti-Cancer Agents in Medicinal Chemistry Endocannabinoid System in Neurological Disorders
Recent Patents on CNS Drug Discovery (Discontinued) Hypoxia-Inducible Factor-1 (HIF-1): A Potential Target for Intervention in Ocular Neovascular Diseases
Current Drug Targets Dual-Specificity MAP Kinase Phosphatases as Targets of Cancer Treatment
Anti-Cancer Agents in Medicinal Chemistry Serum Biochemical Markers of Brain Injury
Mini-Reviews in Medicinal Chemistry PACAP and Its Receptors Exert Pleiotropic Effects in The Nervous System by Activating Multiple Signaling Pathways
Current Protein & Peptide Science Mechanisms Involved in BACE Upregulation Associated to Stress
Current Alzheimer Research Cancer Molecular Imaging: Radionuclide-Based Biomarkers of the Epidermal Growth Factor Receptor (EGFR)
Current Topics in Medicinal Chemistry Recent Advances in Improving Sub-Unit Vaccine Efficacy Using Cytokines as more Specific Immune Inducing Adjuvants
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry A Review on Melatonin’s Effects in Cancer: Potential Mechanisms
Anti-Cancer Agents in Medicinal Chemistry Ras-Induced Resistance to Lapatinib is Overcome by MEK Inhibition
Current Cancer Drug Targets Targeting Telomerase by Antisense-Based Approaches: Perspectives for New Anti-Cancer Therapies
Current Pharmaceutical Design Disintegrins from Snake Venoms and their Applications in Cancer Research and Therapy
Current Protein & Peptide Science Biocompatible Micelles Based on Squalene Portions Linked to PEGylated Polyaspartamide as Potential Colloidal Drug Carriers
Current Nanoscience Critical Roles of EGFR Family Members in Breast Cancer and Breast Cancer Stem Cells: Targets for Therapy
Current Pharmaceutical Design Recent Advances in the Use of Metallic Nanoparticles with Antitumoral Action - Review
Current Medicinal Chemistry