Abstract
There was a major interest in the last years in the design of anticancer agents containing the 1,5-diaryl-3-oxo- 1,4-pentadienyl system. The modification of this pharmacophore by the introduction of an additional Michael acceptor represents a strategy to obtain novel potential antiproliferative agents. In a continuing study of hybrid compounds containing the α-bromoacryloyl moiety as potential anticancer drugs, we synthesized two novel series of hybrids 3a-i and 4a-i, in which this moiety was linked to the 1,5-diaryl-1,4-pentadien-3-one system. Many of the conjugates prepared (3b, 3c and 3g) demonstrated pronounced antiproliferative activity against five cancer cell lines, being more active than the reference compound Melphalan. Compounds 3e and 4b were also examined for their effects on the cell cycle progression of K562 cells. The detection of a sub-G1 peak upon incubation with these compounds suggested that 3e and 4b also exert their growth inhibiting effects by induction of apoptosis.
Keywords: bromoacryloyl moiety, diarylidene ketone, Inhibition of tumor cell growth, Antiproliferative agents, antiproliferative activities, lethal effects, malignant cells, -unsaturated ketones, pharmacophores, Michael acceptors, bromoacrylamido derivative, pyrroloiminoquinone, cytotoxic alkaloids
Letters in Drug Design & Discovery
Title: Design, Synthesis and Biological Evaluation of Hybrid Molecules Containing Conjugated Styryl Ketone and α-Bromoacryloyl Moieties
Volume: 9 Issue: 2
Author(s): Romeo Romagnoli, Pier Giovanni Baraldi, Olga Cruz-Lopez, Maria Kimatrai Salvador, Delia Preti, Mojgan Aghazadeh Tabrizi, Jan Balzarini, Alessandro Canella, Enrica Fabbri and Roberto Gambari
Affiliation:
Keywords: bromoacryloyl moiety, diarylidene ketone, Inhibition of tumor cell growth, Antiproliferative agents, antiproliferative activities, lethal effects, malignant cells, -unsaturated ketones, pharmacophores, Michael acceptors, bromoacrylamido derivative, pyrroloiminoquinone, cytotoxic alkaloids
Abstract: There was a major interest in the last years in the design of anticancer agents containing the 1,5-diaryl-3-oxo- 1,4-pentadienyl system. The modification of this pharmacophore by the introduction of an additional Michael acceptor represents a strategy to obtain novel potential antiproliferative agents. In a continuing study of hybrid compounds containing the α-bromoacryloyl moiety as potential anticancer drugs, we synthesized two novel series of hybrids 3a-i and 4a-i, in which this moiety was linked to the 1,5-diaryl-1,4-pentadien-3-one system. Many of the conjugates prepared (3b, 3c and 3g) demonstrated pronounced antiproliferative activity against five cancer cell lines, being more active than the reference compound Melphalan. Compounds 3e and 4b were also examined for their effects on the cell cycle progression of K562 cells. The detection of a sub-G1 peak upon incubation with these compounds suggested that 3e and 4b also exert their growth inhibiting effects by induction of apoptosis.
Export Options
About this article
Cite this article as:
Romagnoli Romeo, Giovanni Baraldi Pier, Cruz-Lopez Olga, Kimatrai Salvador Maria, Preti Delia, Aghazadeh Tabrizi Mojgan, Balzarini Jan, Canella Alessandro, Fabbri Enrica and Gambari Roberto, Design, Synthesis and Biological Evaluation of Hybrid Molecules Containing Conjugated Styryl Ketone and α-Bromoacryloyl Moieties, Letters in Drug Design & Discovery 2012; 9 (2) . https://dx.doi.org/10.2174/157018012799079842
DOI https://dx.doi.org/10.2174/157018012799079842 |
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
-
HR MAS MR Spectroscopy in Metabolic Characterization of Cancer
Current Topics in Medicinal Chemistry Intracellular Restriction Factors In Mammalian Cells - An Ancient Defense System Finds A Modern Foe
Current HIV Research Current State of ERG as Biomarker in Prostatic Adenocarcinoma
Current Cancer Drug Targets Biomarkers for Systemic Therapy in Ovarian Cancer
Current Cancer Drug Targets The Insulin-Like Growth Factor (IGF) Signaling Pathway: Strategies for Successful Therapeutic Tasks in Cancer Treatment
Current Cancer Therapy Reviews Recent Development in Nano-Sized Dosage Forms of Plant Alkaloid Camptothecin-Derived Drugs
Recent Patents on Anti-Cancer Drug Discovery Novel Concepts in the Development of Platinum Antitumor Drugs
Current Medicinal Chemistry - Anti-Cancer Agents Tumor Angiogenesis and VEGFR-2: Mechanism, Pathways and Current Biological Therapeutic Interventions
Current Drug Metabolism Nanoparticle-based Drug Delivery Systems for Targeted Epigenetics Cancer Therapy
Current Drug Targets Recent Advances in Semisynthesis, Biosynthesis, Biological Activities,Mode of Action, and Structure-Activity Relationship of Podophyllotoxins:An Update (2008-2010)
Mini-Reviews in Medicinal Chemistry Adrenomedullin and Nitric Oxide: Implications for the Etiology and Treatment of Primary Brain Tumors
CNS & Neurological Disorders - Drug Targets Pharmaceutical Measures to Prevent Doxorubicin-Induced Cardiotoxicity
Mini-Reviews in Medicinal Chemistry Nanocarriers in Improving Chemotherapy of Multidrug Resistant Tumors: Key Developments and Perspectives
Current Pharmaceutical Design Plasminogen Activator Inhibitor-1 in Tumor Growth, Angiogenesis and Vascular Remodeling
Current Pharmaceutical Design Medicinal Chemistry Insights into Novel HDAC Inhibitors: An Updated Patent Review (2012-2016)
Recent Patents on Anti-Cancer Drug Discovery The Endoplasmic Reticulum Alpha-Glycosidases as Potential Targets for Virus Control
Current Protein & Peptide Science Recent Patents on Liposomal-Based Chemotherapeutics with a Triggered Release Mechanism
Recent Patents on Nanomedicine A Technological Update of Molecular Diagnostics for Infectious Diseases
Infectious Disorders - Drug Targets Therapeutic Nucleic Acids
Recent Patents on Regenerative Medicine Nanomedicine and its Application in Treatment of Microglia-mediated Neuroinflammation
Current Medicinal Chemistry