Abstract
Identification of novel and selective anticancer agents remains an important and challenging goal in pharmacological research. In search of new compounds with strong antiproliferative activity and simple molecular structure, we have synthesized three different series of compounds in which different substituents were linked to the 3-amino position of the 2-(3, 4, 5-trimethoxybenzoyl)-benzo[b]furan or benzo[b]thiophene ring system. These substituents, corresponding to acetyl/haloacetyl, α-bromoacryloyl and nitrooxyacetyl moieties had different electrophilic properties. The benzoheterocycle parent structures were selected because of their reported bioactivities. Compounds bearing a methoxy group at the 6-position of the benzo[b]furan skeleton, were identified as potent antiproliferative agents against the human chronic myelogenous K562 and murine L1210 leukemia cell lines. Comparison of positional isomers indicated that moving the methoxy group from the 6- to the 5- or 7-position yielded inactive compounds. The effects of a selected series of compounds on cell cycle progression correlated well with their strong antiproliferative activity and inhibition of tubulin polymerization. The analysis of structure-activity relationships observed in the series of compounds described here may represent a platform for the design of more active molecules.
Keywords: Benzo[b]thiophene, Benzo[b]furan, Tumor cell growth, Antiproliferative agents
Letters in Drug Design & Discovery
Title: Synthesis and Evaluation of Haloacetyl, α-Bromoacryloyl and Nitrooxyacetyl Benzo[b]furan and Benzo[b]thiophene Derivatives as Potent Antiproliferative Agents Against Leukemia L1210 and K562 Cells
Volume: 7 Issue: 7
Author(s): Romeo Romagnoli, Pier Giovanni Baraldi, Maria Dora Carrion, Carlota Lopez Cara, Alberto Casolari, Ernest Hamel, Enrica Fabbri and Roberto Gambari
Affiliation:
Keywords: Benzo[b]thiophene, Benzo[b]furan, Tumor cell growth, Antiproliferative agents
Abstract: Identification of novel and selective anticancer agents remains an important and challenging goal in pharmacological research. In search of new compounds with strong antiproliferative activity and simple molecular structure, we have synthesized three different series of compounds in which different substituents were linked to the 3-amino position of the 2-(3, 4, 5-trimethoxybenzoyl)-benzo[b]furan or benzo[b]thiophene ring system. These substituents, corresponding to acetyl/haloacetyl, α-bromoacryloyl and nitrooxyacetyl moieties had different electrophilic properties. The benzoheterocycle parent structures were selected because of their reported bioactivities. Compounds bearing a methoxy group at the 6-position of the benzo[b]furan skeleton, were identified as potent antiproliferative agents against the human chronic myelogenous K562 and murine L1210 leukemia cell lines. Comparison of positional isomers indicated that moving the methoxy group from the 6- to the 5- or 7-position yielded inactive compounds. The effects of a selected series of compounds on cell cycle progression correlated well with their strong antiproliferative activity and inhibition of tubulin polymerization. The analysis of structure-activity relationships observed in the series of compounds described here may represent a platform for the design of more active molecules.
Export Options
About this article
Cite this article as:
Romagnoli Romeo, Giovanni Baraldi Pier, Dora Carrion Maria, Lopez Cara Carlota, Casolari Alberto, Hamel Ernest, Fabbri Enrica and Gambari Roberto, Synthesis and Evaluation of Haloacetyl, α-Bromoacryloyl and Nitrooxyacetyl Benzo[b]furan and Benzo[b]thiophene Derivatives as Potent Antiproliferative Agents Against Leukemia L1210 and K562 Cells, Letters in Drug Design & Discovery 2010; 7 (7) . https://dx.doi.org/10.2174/157018010791526296
DOI https://dx.doi.org/10.2174/157018010791526296 |
Print ISSN 1570-1808 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-628X |
- 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
-
Utility of Assessing Thiopurine S-methyltransferase Polymorphisms Before Azathioprine Therapy
Current Drug Metabolism Preface [Hot topic: Autoimmunity (Executive Editors: D. Stahl and W. Sibrowski)]
Current Pharmaceutical Design Modelling the Neurovascular Unit and the Blood-Brain Barrier with the Unique Function of Pericytes
Current Neurovascular Research Imaging Neuroinflammation in Ischemic Stroke and in the Atherosclerotic Vascular Disease
Current Vascular Pharmacology The Physiological Characteristics and Transcytosis Mechanisms of the Blood-Brain Barrier (BBB)
Current Pharmaceutical Biotechnology RAGE: A Single Receptor for Several Ligands and Different Cellular Responses: The Case of Certain S100 Proteins
Current Molecular Medicine The Role of WNT in Rheumatoid Arthritis and its Therapeutic Implication
Mini-Reviews in Medicinal Chemistry Clinical Assessment of Carotid Atherosclerosis Inflammation by Positron Emission Tomography
Current Molecular Medicine Use of Intravenous Immunoglobulin in the Treatment of Immune-Mediated Demyelinating Diseases of the Nervous System
Current Pharmaceutical Design Adverse Cutaneous Reactions of Systemic Antihistamines
Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents Platelet Activation in Atherogenesis Associated with Low-Grade Inflammation
Inflammation & Allergy - Drug Targets (Discontinued) Anagliptin, A Dipeptidyl Peptidase-4 Inhibitor Ameliorates Arterial Stiffness in Association with Reduction of Remnant-Like Particle Cholesterol and Alanine Transaminase Levels in Type 2 Diabetic Patients
Current Vascular Pharmacology Anticancer Potential of Doxorubicin in Combination with Green-Synthesized Silver Nanoparticle and its Cytotoxicity Effects on Cardio-Myoblast Normal Cells
Anti-Cancer Agents in Medicinal Chemistry Rheumatic Manifestations in Malignancy
Current Rheumatology Reviews Measuring Vasculitis with Numbers: Outcome Scores
Current Rheumatology Reviews The Chemical Defensive System in the Pathobiology of Idiopathic Environment- Associated Diseases
Current Drug Metabolism Recent Advances in the Treatment of Interstitial Lung Disease in Patients with Polymyositis/Dermatomyositis
Endocrine, Metabolic & Immune Disorders - Drug Targets Patent Selections :
Recent Patents on Cardiovascular Drug Discovery Small Molecules as Anti-TNF Drugs
Current Medicinal Chemistry Targeting MET Receptor in Rhabdomyosarcoma: Rationale and Progress
Current Drug Targets