Abstract
DNA damaging agents including anthracyclines, camptothecins and platinum drugs are among most frequently used drugs in the chemotherapeutic routine. Due to their relatively low selectivity for cancer cells, administration of these drugs is associated with adverse side effects, inherent genotoxicity with risk of developing secondary cancers. Development of new drugs, which could be spared of these drawbacks and characterize by improved antitumor efficacy, remains challenging yet vitally important task. These properties are in large part dictated by the selectivity of interaction between the drug and DNA and in this way the studies aimed at elucidating the complex interactions between ligand and DNA represent a key step in the drug development. Studies of the drug-DNA interactions encompass determination of DNA sequence specificity and mode of DNA binding as well as kinetic, dynamic and structural parameters of binding. Here, we consider the types of interactions between small molecule ligands and polynucleotides, how they are affected by DNA sequence and structure, and what is their significance for the antitumor activity. Based on this knowledge, we discuss the wide array of experimental techniques available to researchers for studying drug-DNA interactions, which include absorption and emission spectroscopies, NMR, magnetic and optical tweezers or atomic force microscopy. We show, using the clinical and experimental anticancer drugs as examples, how these methods provide various types of information and at the same time complement each other to provide full picture of drug- DNA interaction and aid in the development of new drugs.
Keywords: Anticancer drug, atomic force microscopy, circular dichroism, DNA, fluorescence, magnetic tweezers, nuclear magnetic resonance.
Current Pharmaceutical Design
Title:Methods for Elucidation of DNA-Anticancer Drug Interactions and their Applications in the Development of New Drugs
Volume: 22 Issue: 44
Author(s): Majus Misiak, Francesco Mantegazza and Giovanni L. Beretta
Affiliation:
Keywords: Anticancer drug, atomic force microscopy, circular dichroism, DNA, fluorescence, magnetic tweezers, nuclear magnetic resonance.
Abstract: DNA damaging agents including anthracyclines, camptothecins and platinum drugs are among most frequently used drugs in the chemotherapeutic routine. Due to their relatively low selectivity for cancer cells, administration of these drugs is associated with adverse side effects, inherent genotoxicity with risk of developing secondary cancers. Development of new drugs, which could be spared of these drawbacks and characterize by improved antitumor efficacy, remains challenging yet vitally important task. These properties are in large part dictated by the selectivity of interaction between the drug and DNA and in this way the studies aimed at elucidating the complex interactions between ligand and DNA represent a key step in the drug development. Studies of the drug-DNA interactions encompass determination of DNA sequence specificity and mode of DNA binding as well as kinetic, dynamic and structural parameters of binding. Here, we consider the types of interactions between small molecule ligands and polynucleotides, how they are affected by DNA sequence and structure, and what is their significance for the antitumor activity. Based on this knowledge, we discuss the wide array of experimental techniques available to researchers for studying drug-DNA interactions, which include absorption and emission spectroscopies, NMR, magnetic and optical tweezers or atomic force microscopy. We show, using the clinical and experimental anticancer drugs as examples, how these methods provide various types of information and at the same time complement each other to provide full picture of drug- DNA interaction and aid in the development of new drugs.
Export Options
About this article
Cite this article as:
Misiak Majus, Mantegazza Francesco and Beretta L. Giovanni, Methods for Elucidation of DNA-Anticancer Drug Interactions and their Applications in the Development of New Drugs, Current Pharmaceutical Design 2016; 22 (44) . https://dx.doi.org/10.2174/1381612822666160831114622
DOI https://dx.doi.org/10.2174/1381612822666160831114622 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...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
-
The Economic Translation of Paradigm-Changing Innovation: A Short History of Biotechnology
Technology Transfer and Entrepreneurship (Discontinued) The Patents on Glucocorticosteroids and Selected New Therapies for the Management of Asthma in Children: Update
Recent Patents on Inflammation & Allergy Drug Discovery Developments in the Application of 1,2,3-Triazoles in Cancer Treatment
Recent Patents on Anti-Cancer Drug Discovery Trefoil Factor Family (TFF) Peptides and their Different Roles in the Mucosal Innate Immune Defense and More: An Update
Current Medicinal Chemistry Metal Based Pharmacological Active Agents: Structural, Electrochemical, DNA Binding Studies and Antibacterial Properties
Current Drug Therapy Immunoadjunctive Therapy against Bacterial Infections Using Herbal Medicines Based on Th17 Cell-mediated Protective Immunity
Current Pharmaceutical Design The Human Trypanolytic Factor: A Drug Shaped Naturally
Infectious Disorders - Drug Targets Endogenous Retroviruses in Domestic Animals
Current Genomics Immunomodulatory Roles of VIP and PACAP in Models of Multiple Sclerosis
Current Pharmaceutical Design Designing and Testing New Therapeutic Modalities for Treatment of Inflammatory Bowel Disease: Role of Experimental Animal Models
Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents Organic Cation Transporters: Physiology, Toxicology and Special Focus on Ethidium as a Novel Substrate
Current Drug Metabolism Gamma-Oryzanol – A Multi-Purpose Steryl Ferulate
Current Nutrition & Food Science Adeno-Associated Viral Vector Mediated Expression of Broadly- Neutralizing Antibodies Against HIV-Hitting a Fast-Moving Target
Current HIV Research Estrogen, A Double-Edged Sword: Modulation of TH1- and TH2-Mediated Inflammations by Differential Regulation of TH1 / TH2 Cytokine Production
Current Drug Targets - Inflammation & Allergy Costimulation, Coinhibition and Cancer
Current Cancer Drug Targets Pharmaco-Therapeutic Challenges in Cancer Biology with Focus on the Immune- System Related Risk Factors
Current Pharmaceutical Design Insight View on Possible Role of Fluoroquinolones in Cancer Therapy
Current Topics in Medicinal Chemistry The Potential of Ellagic Acid as a Possible Antimalarial Drug Candidate
Current Bioactive Compounds Macrophage-Assisted Inflammation and Pharmacological Regulation of the Cholinergic Anti-Inflammatory Pathway
Current Medicinal Chemistry Erythropoietin: New Approaches to Improved Molecular Designs and Therapeutic Alternatives
Current Pharmaceutical Design