Abstract
DNA-binding compounds are of extraordinary importance in medicine, accounting for a substantial portion of antitumor drugs in clinical usage. However, their mechanisms of action remain sometimes incompletely understood. This review critically examines two broad classes of molecules that bind noncovalently to DNA: intercalators and groove binders. Intercalators bind to DNA by inserting their chromophore moiety between two consecutive base pairs, whereas groove binders fit into the grooves of DNA. Noncovalent DNAinteractive drugs can recognize certain supramolecular DNA structures such as the Gquadruplexes found in telomeres and in numerous gene promoters, and they can act as topoisomerase I and II poisons. We discuss how DNA-binding compounds affect transcription and compete with protein factors for binding to consensus binding sites in gene promoters both in vitro and in cultured cancer cells. Moreover, we comment on the design of molecules that can tightly and specifically bind to any desired target DNA, such as various hairpin polyamides which efficacy as chemotherapeutic agents is being evaluated. At present, genome-wide studies, which provide details of events that may influence both cancer progression and therapeutic outcome, are a common way used to analyze the effects of DNA-binding compounds. A conclusive feature that emerges from reviewing the information on DNA-binding compounds is that both natural sources and chemical approaches can be productively used to obtain drugs to manipulate gene expression in cancer cells.
Keywords: Antitumor chemotherapy, DNA-binding drugs, DNA recognition, Drug discovery, Mechanism of action, Sequence specificity.
Current Medicinal Chemistry
Title:Noncovalent Binding to DNA: Still a Target in Developing Anticancer Agents
Volume: 23 Issue: 36
Author(s): José Portugal and Francisca Barceló
Affiliation:
Keywords: Antitumor chemotherapy, DNA-binding drugs, DNA recognition, Drug discovery, Mechanism of action, Sequence specificity.
Abstract: DNA-binding compounds are of extraordinary importance in medicine, accounting for a substantial portion of antitumor drugs in clinical usage. However, their mechanisms of action remain sometimes incompletely understood. This review critically examines two broad classes of molecules that bind noncovalently to DNA: intercalators and groove binders. Intercalators bind to DNA by inserting their chromophore moiety between two consecutive base pairs, whereas groove binders fit into the grooves of DNA. Noncovalent DNAinteractive drugs can recognize certain supramolecular DNA structures such as the Gquadruplexes found in telomeres and in numerous gene promoters, and they can act as topoisomerase I and II poisons. We discuss how DNA-binding compounds affect transcription and compete with protein factors for binding to consensus binding sites in gene promoters both in vitro and in cultured cancer cells. Moreover, we comment on the design of molecules that can tightly and specifically bind to any desired target DNA, such as various hairpin polyamides which efficacy as chemotherapeutic agents is being evaluated. At present, genome-wide studies, which provide details of events that may influence both cancer progression and therapeutic outcome, are a common way used to analyze the effects of DNA-binding compounds. A conclusive feature that emerges from reviewing the information on DNA-binding compounds is that both natural sources and chemical approaches can be productively used to obtain drugs to manipulate gene expression in cancer cells.
Export Options
About this article
Cite this article as:
Portugal José and Barceló Francisca, Noncovalent Binding to DNA: Still a Target in Developing Anticancer Agents, Current Medicinal Chemistry 2016; 23 (36) . https://dx.doi.org/10.2174/0929867323666160902153511
DOI https://dx.doi.org/10.2174/0929867323666160902153511 |
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
-
Histone Deacetylase Inhibitors: A New Wave of Molecular Targeted Anticancer Agents
Recent Patents on Anti-Cancer Drug Discovery Optimization of Lentiviral Vectors Generation for Biomedical and Clinical Research Purposes: Contemporary Trends in Technology Development and Applications
Current Gene Therapy Understanding Autophagy in Cell Death Control
Current Pharmaceutical Design Retroviral Gene Therapy: Safety Issues and Possible Solutions
Current Gene Therapy Small Interfering RNA for Effective Cancer Therapies
Mini-Reviews in Medicinal Chemistry Withdrawal Notice: The Recent Advancement in the Field of Super Paramagnetic Iron Oxide Nanoparticles (SPIONs) for Aiming Breast Cancer
Current Drug Metabolism Is the Expression of Deoxynucleoside Kinases and 5'-nucleotidases in Animal Tissues Related to the Biological Effects of Nucleoside Analogs?
Current Medicinal Chemistry Fighting Tumor Cell Survival: Advances in the Design and Evaluation of Pim Inhibitors
Current Medicinal Chemistry Recent Research Trends on Bismuth Compounds in Cancer Chemoand Radiotherapy
Current Medicinal Chemistry Recent Advance in the Research of Flavonoids as Anticancer Agents
Mini-Reviews in Medicinal Chemistry Gene Therapy Approaches in an Autoimmune Demyelinating Disease: Multiple Sclerosis
Current Gene Therapy Brain Tumour Stem Cells: Implications for Cancer Therapy and Regenerative Medicine
Current Stem Cell Research & Therapy Embryonic Stem Cell MicroRNAs: Defining Factors in Induced Pluripotent (iPS) and Cancer (CSC) Stem Cells?
Current Stem Cell Research & Therapy Paving Roads for New Drugs in Oncology
Recent Patents on Anti-Cancer Drug Discovery Bombacaceae Between the Ethnomedical Uses and Pharmacological Evidences: A Review
The Natural Products Journal Current Progresses in Metal-based Anticancer Complexes as Mammalian TrxR Inhibitors
Anti-Cancer Agents in Medicinal Chemistry Drugs, Environmental Factors, Loci and Genes Involved in Nonsyndromic Orofacial Cleft
Current Pharmacogenomics On the Power of Additional and Complex Chromosomal Aberrations in CML
Current Genomics Proteasome Inhibitors and Modulators of Angiogenesis in Multiple Myeloma
Current Medicinal Chemistry Heterocyclic Secretase Inhibitors for the Treatment of Alzheimer’s Disease: An Overview
Central Nervous System Agents in Medicinal Chemistry