Abstract
The minor-groove is an important receptor for enzymes and proteins involved in the processing and expression of genomic DNA. Small molecules capable of interfering with these processes by virtue of their ability to form adducts within the recognition sequences targeted by these enzymes/proteins have potential applications as cytotoxic and generegulating agents. Until recently, the targeting of the minor groove by platinum-based agents has been a widely unexplored opportunity. As part of this focused review on irreversible minor-groove modifying agents acting on adenine-N3, we summarize work performed in our laboratory and by our collaborators on a novel platinum-acridine conjugate, PTACRAMTU ([PtCl(en)(ACRAMTU)](NO3)2, en = ethane-1,2-diamine, ACRAMTU = 1-[2-(acridin-9-ylamino)ethyl]-1,3- dimethylthiourea, acridinium cation). The design of this agent as a non-cisplatin type pharmacophore has led to a groundbreaking discovery, the unprecedented intercalator-driven formation of platinum-adenine-N3 adducts in the minor groove of DNA. The minor-groove reactivity of PT-ACRAMTU represents a new paradigm in platinum-DNA interactions, which opens new avenues in the design of platinum-based therapeutics acting by a mechanism different from that of agents currently in clinical use.
Keywords: Platinum drugs, intercalators, minor-groove binders, cancer chemotherapy, adenine, transcription factor, acridine
Anti-Cancer Agents in Medicinal Chemistry
Title: Adenine-N3 in the DNA Minor Groove - An Emerging Target for Platinum Containing Anticancer Pharmacophores
Volume: 7 Issue: 1
Author(s): Rajsekhar Guddneppanavar and Ulrich Bierbach
Affiliation:
Keywords: Platinum drugs, intercalators, minor-groove binders, cancer chemotherapy, adenine, transcription factor, acridine
Abstract: The minor-groove is an important receptor for enzymes and proteins involved in the processing and expression of genomic DNA. Small molecules capable of interfering with these processes by virtue of their ability to form adducts within the recognition sequences targeted by these enzymes/proteins have potential applications as cytotoxic and generegulating agents. Until recently, the targeting of the minor groove by platinum-based agents has been a widely unexplored opportunity. As part of this focused review on irreversible minor-groove modifying agents acting on adenine-N3, we summarize work performed in our laboratory and by our collaborators on a novel platinum-acridine conjugate, PTACRAMTU ([PtCl(en)(ACRAMTU)](NO3)2, en = ethane-1,2-diamine, ACRAMTU = 1-[2-(acridin-9-ylamino)ethyl]-1,3- dimethylthiourea, acridinium cation). The design of this agent as a non-cisplatin type pharmacophore has led to a groundbreaking discovery, the unprecedented intercalator-driven formation of platinum-adenine-N3 adducts in the minor groove of DNA. The minor-groove reactivity of PT-ACRAMTU represents a new paradigm in platinum-DNA interactions, which opens new avenues in the design of platinum-based therapeutics acting by a mechanism different from that of agents currently in clinical use.
Export Options
About this article
Cite this article as:
Guddneppanavar Rajsekhar and Bierbach Ulrich, Adenine-N3 in the DNA Minor Groove - An Emerging Target for Platinum Containing Anticancer Pharmacophores, Anti-Cancer Agents in Medicinal Chemistry 2007; 7 (1) . https://dx.doi.org/10.2174/187152007779313991
DOI https://dx.doi.org/10.2174/187152007779313991 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
Call for Papers in Thematic Issues
Induction of cell death in cancer cells by modulating telomerase activity using small molecule drugs
Telomeres are distinctive but short stretches present at the corners of chromosomes and aid in stabilizing chromosomal makeup. Resynthesis of telomeres supported by the activity of reverse transcriptase ribonucleoprotein complex telomerase. There is no any telomerase activity in human somatic cells, but the stem cells and germ cells undergone telomerase ...read more
Role of natural compounds as anti anti-cancer agents
Cancer is considered the leading cause of worldwide mortality, accounting for nearly 10 million deaths in 2022. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy remains an important approach in treatment o f several types of cancers, even though ...read more
Signaling and enzymatic modulators in cancer treatment
Cancer accounts for nearly 10 million deaths in 2022 and is considered the leading cause of worldwide mortality. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy, radiotherapy and surgery are the most important approach for the treatment of several ...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
Related Articles
-
Recent Nanocarrier Approaches for Targeted Drug Delivery in Cancer Therapy
Current Molecular Pharmacology Polymer Coated Iron Nanoparticles: Radiolabeling & In vitro Studies
Current Radiopharmaceuticals Immunological Mechanism and Clinical Application of PAMP Adjuvants
Recent Patents on Anti-Cancer Drug Discovery Detection of Predictive Markers for Therapeutic Stratification of Salivary Glands Tumors
Current Drug Targets Role of ABC Transporters in Veterinary Medicine: Pharmaco- Toxicological Implications
Current Medicinal Chemistry Recent Patents in Antiviral siRNAs
Recent Patents on Anti-Infective Drug Discovery Cholangiocarcinoma Therapeutics: An Update
Current Cancer Drug Targets CT Image Reconstruction Using NLMfuzzyCD Regularization Method
Current Medical Imaging Potentiation of Anti-Cancer Treatment by Modulators of Energy Metabolism
Current Pharmaceutical Biotechnology Editorial [ Hot Topic: Targeting Tumor Angiogenesis: An Update (Guest Editor: Girolamo Ranieri)]
Current Medicinal Chemistry The Urokinase Receptor and its Structural Homologue C4.4A in Human Cancer: Expression, Prognosis and Pharmacological Inhibition
Current Medicinal Chemistry Current and Future Treatment Options in Idiopathic Pulmonary Fibrosis
Inflammation & Allergy - Drug Targets (Discontinued) Green Tea Polyphenols as Proteasome Inhibitors: Implication in Chemoprevention
Current Cancer Drug Targets Malignant Hypercalcemia
Current Medicinal Chemistry Nimesulide is a Selective COX-2 Inhibitory, Atypical Non-Steroidal Anti-Inflammatory Drug
Current Medicinal Chemistry Advances in DNA-Ligands with Groove Binding, Intercalating and/or Alkylating Activity: Chemistry, DNA-Binding and Biology
Current Medicinal Chemistry Medicinal Chemistry Insights into Novel HDAC Inhibitors: An Updated Patent Review (2012-2016)
Recent Patents on Anti-Cancer Drug Discovery CRISPR/Cas9 Genome Editing Tool: A Promising Tool for Therapeutic Applications on Respiratory Diseases
Current Gene Therapy Tissue-Based Approaches to Study Pharmacodynamic Endpoints in Early Phase Oncology Clinical Trials
Current Drug Targets Paving Roads for New Drugs in Oncology
Recent Patents on Anti-Cancer Drug Discovery