Abstract
There is a currently growing interest in the development of histone deacetylase inhibitors (HDACs) as anticancer agents. Histone deacetylases are critically important in the functional regulation of gene transcription as well as in chromatin structure remodeling. A number of small molecule inhibitors of HDAC, such as the naturally occurring trichostatin A (TSA), as well as synthetic compounds, such as suberoylanilide hydroxamic acid (SAHA), scriptaid, oxamflatin or MS-275, have been reported to induce differentiation of several cancer cell lines and suppress cell proliferation. This article will review the recent progress being made in our laboratories in the development of two new families of potent HDAC inhibitors: sulfonamide hydroxamic acids and anilides, as well as TSA-like straight chain derivatives. Some of these compounds inhibit partially purified recombinant human HDAC enzymes with IC50s in the micromolar to low nanomolar range and can induce hyperacetylation of histones in human cancer cells. These compounds significantly inhibit proliferation, induce expression of p21WAF1 / Cip1, and cause cell cycle arrest in various human cancer cells. The lead candidates were screened in a panel of human tumor and normal cell lines. The inhibition of HDAC activity represents a novel approach for intervening in cell cycle regulation and may be used in future cancer therapies. The structure-activity relationships, the antiproliferative activity and the in vivo efficacy are discussed.
Keywords: hydroxamate, anilide derivatives, histone deacetylase inhibitors, anticancer agents, hdacs, trichostatin a, tsa, suberoylanilide hydroxamic acid, hdac enzymes, structure-activity relationships
Current Medicinal Chemistry
Title: Novel Hydroxamate and Anilide Derivatives as Potent Histone Deacetylase Inhibitors: Synthesis and Antiproliferative Evaluation
Volume: 10 Issue: 22
Author(s): Giliane Bouchain and Daniel Delorme
Affiliation:
Keywords: hydroxamate, anilide derivatives, histone deacetylase inhibitors, anticancer agents, hdacs, trichostatin a, tsa, suberoylanilide hydroxamic acid, hdac enzymes, structure-activity relationships
Abstract: There is a currently growing interest in the development of histone deacetylase inhibitors (HDACs) as anticancer agents. Histone deacetylases are critically important in the functional regulation of gene transcription as well as in chromatin structure remodeling. A number of small molecule inhibitors of HDAC, such as the naturally occurring trichostatin A (TSA), as well as synthetic compounds, such as suberoylanilide hydroxamic acid (SAHA), scriptaid, oxamflatin or MS-275, have been reported to induce differentiation of several cancer cell lines and suppress cell proliferation. This article will review the recent progress being made in our laboratories in the development of two new families of potent HDAC inhibitors: sulfonamide hydroxamic acids and anilides, as well as TSA-like straight chain derivatives. Some of these compounds inhibit partially purified recombinant human HDAC enzymes with IC50s in the micromolar to low nanomolar range and can induce hyperacetylation of histones in human cancer cells. These compounds significantly inhibit proliferation, induce expression of p21WAF1 / Cip1, and cause cell cycle arrest in various human cancer cells. The lead candidates were screened in a panel of human tumor and normal cell lines. The inhibition of HDAC activity represents a novel approach for intervening in cell cycle regulation and may be used in future cancer therapies. The structure-activity relationships, the antiproliferative activity and the in vivo efficacy are discussed.
Export Options
About this article
Cite this article as:
Bouchain Giliane and Delorme Daniel, Novel Hydroxamate and Anilide Derivatives as Potent Histone Deacetylase Inhibitors: Synthesis and Antiproliferative Evaluation, Current Medicinal Chemistry 2003; 10 (22) . https://dx.doi.org/10.2174/0929867033456585
DOI https://dx.doi.org/10.2174/0929867033456585 |
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
-
Stress-Activated MAP Kinase Cascades in Cellular Senescence
Current Medicinal Chemistry Multidrug Transporters as Drug Targets
Current Drug Targets The Potential Health Benefits of Algae and Micro Algae in Medicine: A Review on Spirulina platensis
Current Nutrition & Food Science Survivin as a Prognostic/Predictive Marker and Molecular Target in Cancer Therapy
Current Medicinal Chemistry Leukaemia Infection Diagnosis and Intestinal Flora Disorder
Current Molecular Medicine Lung Defence Mechanisms and Their Potential Role in the Prevention of Ventilator Associated Pneumonia
Current Respiratory Medicine Reviews Knemometry for Assessment of Growth Suppressive Effects of Exogenous Glucocorticoids
Current Pediatric Reviews Chalcone-Coumarin Derivatives as Potential Anti-Cancer Drugs: An in vitro and in vivo Investigation
Anti-Cancer Agents in Medicinal Chemistry The Application of Fungal Beta-glucans for the Treatment of Colon Cancer
Anti-Cancer Agents in Medicinal Chemistry Phosphorylation-Specific Prolyl Isomerase Pin1 as a new Diagnostic and Therapeutic Target for Cancer
Current Cancer Drug Targets Determinants of Left Ventricular Hypertrophy
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Molecular Modeling, Docking, Dynamics and Simulation of Gefitinib and its Derivatives with EGFR in Non-small Cell Lung Cancer
Current Computer-Aided Drug Design Dietary Fatty Acids in Metabolic Syndrome, Diabetes and Cardiovascular Diseases
Current Diabetes Reviews Lung Cancer Brachytherapy: Robotics-Assisted Minimally Invasive Approach
Current Respiratory Medicine Reviews Evaluation of Angiogenesis with the Expression of VEGF-C and CD34 in Human Colon Cancer
Current Chemical Biology Chemoinformatic Analysis of Biologically Active Macrocycles
Current Topics in Medicinal Chemistry Cationicity and Hydrophobicity Enhance the Cytotoxic Potency of Phoratoxin C Anticancer Peptide Analogues against Triple Negative Breast Cancer Cells
Current Bioactive Compounds Bioplex Technology: Novel Synthetic Gene Delivery Pharmaceutical Based on Peptides Anchored to Nucleic Acids
Current Pharmaceutical Design 4-Oxothiazolidines with Exocyclic C=C Double Bond(s): Synthesis, Structure, Reactions and Biological Activity
Current Organic Chemistry Patent Selections
Recent Patents on Biomarkers