Abstract
Novel 5,6-disubstituted pyridazin-3(2H)-one derivatives were designed and synthesized as combretastatin A-4 analogues. Our objective was to overcome the spontaneous cis to trans isomerization of the compound. We therefore replaced the cis-double bond with a pyridazine ring. The antiproliferative activity of the novel analogues was evaluated against four human cancer cell lines (HL-60, MDAMB- 435, SF-295 and HCT-8). We found that the analogues had little activity either against selected cell lines or against purified tubulin. Molecular modeling studies may account for their inactivity.
Keywords: Pyridazine, Combretastatin A-4, Cytotoxicity, Suzuki-Miyaura cross coupling, Anticancer agent and Tubulin activity.
Anti-Cancer Agents in Medicinal Chemistry
Title:Synthesis and Antiproliferative Effects of 5,6-Disubstituted Pyridazin-3(2H)-ones Designed as Conformationally Constrained Combretastatin A-4 Analogues
Volume: 13 Issue: 7
Author(s): Mohamed Elagawany, Martine Schmitt, Adel Ghiaty, A. Sh. El-Etrawy, Mohamed A. Ibrahim, Frederic Bihel, Aline Borba Sbardelotto, Claudia Pessoa, Tam Luong Nguyen, Ernest Hamel and Jean Jacques Bourguignon
Affiliation:
Keywords: Pyridazine, Combretastatin A-4, Cytotoxicity, Suzuki-Miyaura cross coupling, Anticancer agent and Tubulin activity.
Abstract: Novel 5,6-disubstituted pyridazin-3(2H)-one derivatives were designed and synthesized as combretastatin A-4 analogues. Our objective was to overcome the spontaneous cis to trans isomerization of the compound. We therefore replaced the cis-double bond with a pyridazine ring. The antiproliferative activity of the novel analogues was evaluated against four human cancer cell lines (HL-60, MDAMB- 435, SF-295 and HCT-8). We found that the analogues had little activity either against selected cell lines or against purified tubulin. Molecular modeling studies may account for their inactivity.
Export Options
About this article
Cite this article as:
Elagawany Mohamed, Schmitt Martine, Ghiaty Adel, El-Etrawy Sh. A., Ibrahim A. Mohamed, Bihel Frederic, Sbardelotto Borba Aline, Pessoa Claudia, Nguyen Luong Tam, Hamel Ernest and Bourguignon Jacques Jean, Synthesis and Antiproliferative Effects of 5,6-Disubstituted Pyridazin-3(2H)-ones Designed as Conformationally Constrained Combretastatin A-4 Analogues, Anti-Cancer Agents in Medicinal Chemistry 2013; 13 (7) . https://dx.doi.org/10.2174/1871520611313070018
DOI https://dx.doi.org/10.2174/1871520611313070018 |
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
-
Dequalinium-Derived Nanoconstructs: A Promising Vehicle for Mitochondrial Targeting
Current Drug Delivery “Smart” Nanocarriers: A New Paradigm for Tumor Targeting Drug Delivery Systems
Drug Delivery Letters Microwave-Assisted Synthesis of Pyrazinamide Derivatives: The Coupling Reaction of 3-Chloropyrazine-2-Carboxamide and Ring-Substituted Anilines
Current Organic Synthesis The NK-1 Receptor: A New Target in Cancer Therapy
Current Drug Targets Photoacoustic Detection and Imaging of Cancer Using Nanoparticles as Optical Contrast Agents
Recent Patents on Nanomedicine Effects of Hyperlipidemia and Cardiovascular Diseases on Proliferation, Differentiation and Homing of Mesenchymal Stem Cells
Current Stem Cell Research & Therapy Prolylcarboxypeptidase Gene Expression in the Heart and Kidney: Effects of Obesity and Diabetes
Cardiovascular & Hematological Agents in Medicinal Chemistry Withdrawal Notice: Vilsmeier-Haack Cyclisation as A Facile Synthetic Route to Thieno [2,3-b] quinolines (Part I)
Letters in Organic Chemistry The Significant Role of Nutraceutical Compounds in Ulcerative Colitis Treatment
Current Medicinal Chemistry Particulate Systems Based on Poly(Lactic-co-Glycolic)Acid (pLGA) for Immunotherapy of Cancer
Current Pharmaceutical Design Small Molecular Inhibitors Targeting Chromatin Regulating Proteins for Cancer
Current Protein & Peptide Science Nerve Growth Factor Receptors and Signaling in Breast Cancer
Current Cancer Drug Targets Therapeutic Targets for Metastatic Prostate Cancer
Current Drug Targets Synthetic and Natural Coumarins as Cytotoxic Agents
Current Medicinal Chemistry - Anti-Cancer Agents Phytoestrogens and other Botanicals: On the Problems of Evidence-based Evaluation
Recent Patents on Cardiovascular Drug Discovery A Common Biological Mechanism in Cancer and Alzheimers Disease?
Current Alzheimer Research Eriocalyxin B-Induced Apoptosis in Pancreatic Adenocarcinoma Cells Through Thiol-Containing Antioxidant Systems and Downstream Signalling Pathways
Current Molecular Medicine Inflammasome, Inflammation and Cancer: An Interrelated Pathobiological Triad
Current Drug Targets Role of Stem Cells in Colorectal Cancer Progression and Prognostic and Predictive Characteristics of Stem Cell Markers in Colorectal Cancer
Current Stem Cell Research & Therapy The Structure and Function of Histone Deacetylases: The Target for Anti-cancer Therapy
Current Medicinal Chemistry