Abstract
Nucleic acids are prone to structural polymorphism and a number of structures may be formed in addition to the well-known DNA double helix. Among these is a family of nucleic acid four-stranded structures known as G-quadruplexes (G4). These quadruplex structures can be formed by sequences containing repetitive guanine-rich tracks and the analysis of Non-B-DNA database indicated an enrichment of these sequences in genomic regions controlling cellular proliferation, such as for example in the promoter regions of c- MYC, k-RAS, c-KIT, HSP90 and VEGF among others. The broad concept of G4 targeting with small molecules is now generally accepted as a promising novel approach to anticancer therapy and several small molecules with antiproliferative activity in cancer cell lines have also been shown to stabilize these DNA structures, thus suggesting a potential application of G4-interactive small molecules as new anticancer drugs. Herein we review, by targeted oncogene and main chemical scaffold, those G4-interactive small molecules with reported gene expression modulatory activity in cancer cell lines. The data obtained so far are encouraging but further efforts are needed to validate G4 as drug targets and optimize the structure of G4- interactive small molecules into new anticancer drugs.
Keywords: Anticancer, oncogenes, transcriptional regulation, quadruplexes, DNA, indoloquinolines, porphyrins, drug target.
Current Medicinal Chemistry
Title:Oncogene Expression Modulation in Cancer Cell Lines by DNA G-Quadruplex-Interactive Small Molecules
Volume: 24 Issue: 42
Author(s): Ana Paula Francisco and Alexandra Paulo*
Affiliation:
- Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa; Av. Prof. Gama Pinto, 1649 003 Lisbon,Portugal
Keywords: Anticancer, oncogenes, transcriptional regulation, quadruplexes, DNA, indoloquinolines, porphyrins, drug target.
Abstract: Nucleic acids are prone to structural polymorphism and a number of structures may be formed in addition to the well-known DNA double helix. Among these is a family of nucleic acid four-stranded structures known as G-quadruplexes (G4). These quadruplex structures can be formed by sequences containing repetitive guanine-rich tracks and the analysis of Non-B-DNA database indicated an enrichment of these sequences in genomic regions controlling cellular proliferation, such as for example in the promoter regions of c- MYC, k-RAS, c-KIT, HSP90 and VEGF among others. The broad concept of G4 targeting with small molecules is now generally accepted as a promising novel approach to anticancer therapy and several small molecules with antiproliferative activity in cancer cell lines have also been shown to stabilize these DNA structures, thus suggesting a potential application of G4-interactive small molecules as new anticancer drugs. Herein we review, by targeted oncogene and main chemical scaffold, those G4-interactive small molecules with reported gene expression modulatory activity in cancer cell lines. The data obtained so far are encouraging but further efforts are needed to validate G4 as drug targets and optimize the structure of G4- interactive small molecules into new anticancer drugs.
Export Options
About this article
Cite this article as:
Francisco Paula Ana and Paulo Alexandra*, Oncogene Expression Modulation in Cancer Cell Lines by DNA G-Quadruplex-Interactive Small Molecules, Current Medicinal Chemistry 2017; 24 (42) . https://dx.doi.org/10.2174/0929867323666160829145055
DOI https://dx.doi.org/10.2174/0929867323666160829145055 |
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
![](/images/wayfinder.jpg)
- 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
-
Inventions Designed to Enhance Drug Delivery Across Epithelial and Endothelial Cells Through the Paracellular Pathway
Recent Patents on Drug Delivery & Formulation Prostaglandin E<sub>2</sub> Receptor 4 (EP4): A Promising Therapeutic Target for the Treatment of Cancer and Inflammatory Diseases
Current Chemical Biology Modified Polysaccharides as Carriers for Biomolecules
Pharmaceutical Nanotechnology Metal Toxicity and Speciation: A Review
Current Medicinal Chemistry Emerging Features in the Regulation of MMP-9 Gene Expression for the Development of Novel Molecular Targets and Therapeutic Strategies
Current Drug Targets - Inflammation & Allergy Saccharomyces Cerevisiae as a Genetic Model in Anticancer Therapy
Current Pharmacogenomics Biological Activities of Yarrow Species (Achillea spp.)
Current Pharmaceutical Design Androgen Pathway Related Gene Variants and Prostate Cancer Association in Auckland Men
Current Pharmacogenomics and Personalized Medicine Isothiocyanates as Cancer Chemopreventive Agents: Their Biological Activities and Metabolism in Rodents and Humans
Current Drug Metabolism Exploring Mechanisms of MicroRNA Downregulation in Cancer
MicroRNA Antimicrobial, In Vitro and In Vivo Antineoplastic Activities, Mechanism of Action, Structural and Thermal Properties of a Small-Novel Pharmaceutical Organometallic Chelate
Mini-Reviews in Medicinal Chemistry Modulation of Prion by Small Molecules: From Monovalent to Bivalent and Multivalent Ligands
Current Topics in Medicinal Chemistry Beneficial Extracardiac Effects of Cardiovascular Medications
Current Cardiology Reviews Muscarinic Receptors as Targets for Metronomic Therapy in Breast Cancer
Current Pharmaceutical Design Advanced Platelet-Rich Fibrin Extract Treatment Promotes the Proliferation and Differentiation of Human Adipose-Derived Mesenchymal Stem Cells through Activation of Tryptophan Metabolism
Current Stem Cell Research & Therapy Do Drugs Work for ΟΑΒ Following Prostate Cancer Surgery
Current Drug Targets CD147/EMMPRIN and CD44 are Potential Therapeutic Targets for Metastatic Prostate Cancer
Current Cancer Drug Targets Rational Combination of Targeted Therapies As A Strategy to Overcome The Mechanisms of Resistance to Inhibitors of EGFR Signaling
Current Pharmaceutical Design Immunological Aspects of the Prostate Gland and Related Diseases
Current Immunology Reviews (Discontinued) Meet Our Editorial Board Member
Clinical Immunology, Endocrine & Metabolic Drugs (Discontinued)