Abstract
Cis-diamminedichloroplatinum(II) (cisplatin) is widely used for the treatment of testicular, ovarian, and other forms of cancer. Several second generation platinum centered antitumor drugs have been approved or undergoing phase-3 clinical trial. Cisplatin arrests the cell cycle at the G2 phase by a mechanism commonly known as apoptosis. At the molecular level, it is generally believed that the anticancer properties of these compounds are due to the covalent binding to DNA. In addition to DNA binding, the platinum drugs bind and interact with proteins and enzymes. The toxic effects of the drugs have been usually attributed to protein binding. However, a growing body of work points to much more complex anticancer mechanisms involving direct and indirect interactions of platinum compounds with proteins and enzymes. In this review, a discussion on the strength and weaknesses of DNA binding mechanism followed by enzymes and protein interactions with the drugs are presented for the comprehensive understand ing of apoptosis. The purpose of this review is to encourage researchers to explore metallobiochemistry of platinum drugs focusing attention to cellular and molecular events beyond DNA binding.
Keywords: cisplatin, dna polymerases
Mini-Reviews in Medicinal Chemistry
Title: Biomolecular Targets for Platinum Antitumor Drugs
Volume: 2 Issue: 2
Author(s): Rathindra N. Bose
Affiliation:
Keywords: cisplatin, dna polymerases
Abstract: Cis-diamminedichloroplatinum(II) (cisplatin) is widely used for the treatment of testicular, ovarian, and other forms of cancer. Several second generation platinum centered antitumor drugs have been approved or undergoing phase-3 clinical trial. Cisplatin arrests the cell cycle at the G2 phase by a mechanism commonly known as apoptosis. At the molecular level, it is generally believed that the anticancer properties of these compounds are due to the covalent binding to DNA. In addition to DNA binding, the platinum drugs bind and interact with proteins and enzymes. The toxic effects of the drugs have been usually attributed to protein binding. However, a growing body of work points to much more complex anticancer mechanisms involving direct and indirect interactions of platinum compounds with proteins and enzymes. In this review, a discussion on the strength and weaknesses of DNA binding mechanism followed by enzymes and protein interactions with the drugs are presented for the comprehensive understand ing of apoptosis. The purpose of this review is to encourage researchers to explore metallobiochemistry of platinum drugs focusing attention to cellular and molecular events beyond DNA binding.
Export Options
About this article
Cite this article as:
Bose N. Rathindra, Biomolecular Targets for Platinum Antitumor Drugs, Mini-Reviews in Medicinal Chemistry 2002; 2 (2) . https://dx.doi.org/10.2174/1389557024605500
DOI https://dx.doi.org/10.2174/1389557024605500 |
Print ISSN 1389-5575 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5607 |
Call for Papers in Thematic Issues
Bioprospecting of Natural Products as Sources of New Multitarget Therapies
According to the Convention on Biological Diversity, bioprospecting is the exploration of biodiversity and indigenous knowledge to develop commercially valuable products for pharmaceutical and other applications. Bioprospecting involves searching for useful organic compounds in plants, fungi, marine organisms, and microorganisms. Natural products traditionally constituted the primary source of more than ...read more
Computational Frontiers in Medicinal Chemistry
The thematic issue "Computational Frontiers in Medicinal Chemistry" provides a robust platform for delving into state-of-the-art computational methodologies and technologies that significantly propel advancements in medicinal chemistry. This edition seeks to amalgamate top-tier reviews spotlighting the latest trends and breakthroughs in the fusion of computational approaches, including artificial intelligence (AI) ...read more
Natural Products and Dietary Supplements in Alleviation of Metabolic, Cardiovascular, and Neurological Disorders
Metabolic disorders like diabetes, obesity, inflammation, oxidative stress, cancer etc, cardiovascular disorders like angina, myocardial infarction, congestive heart failure etc as well as neurological disorders like Alzheimer?s, Parkinson?s, Epilepsy, Depression, etc are the global burden. They covered the major segment of the diseases and disorders from which the human community ...read more
Natural Products in Drug Discovery
Natural products have always been one of the important ways of drug discovery due to their novel skeleton and diverse functional group characteristics. According to statistics, between 1981 and 2019, the FDA approved a total of 1,394 small molecule drugs for marketing, of which 930 marketed drugs originated from the ...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
-
Preparation, Characterization and <i>In Vitro</i> Antioxidant Potential of Boldine-phospholipid Complex
Current Drug Therapy Repurposing Chloroquine Analogs as an Adjuvant Cancer Therapy
Recent Patents on Anti-Cancer Drug Discovery Theranostics for Cancer Therapy
Current Drug Delivery Current Concepts on Cardiovascular Stent Devices
Mini-Reviews in Medicinal Chemistry Immunotherapeutic Impact of Toll-like Receptor Agonists in Breast Cancer
Anti-Cancer Agents in Medicinal Chemistry Recent Advances in Antibody-Drug Conjugates for Breast Cancer Treatment
Current Medicinal Chemistry Lumiflavin Enhances the Effects of Ionising Radiation on Ovarian Cancer Stem-Like Cells by Inhibiting Autophagy
Anti-Cancer Agents in Medicinal Chemistry Potential Utilization of Bystander / Abscopal-Mediated Signal Transduction Events in the Treatment of Solid Tumors
Current Signal Transduction Therapy Inhibition of Cdc42-Interacting Protein 4 (CIP4) Impairs Osteosarcoma Tumor Progression
Current Cancer Drug Targets Radiolabeled Probes Targeting Tyrosine-Kinase Receptors For Personalized Medicine
Current Pharmaceutical Design Multi-Targeted Natural Products Evaluation Based on Biological Activity Prediction with PASS
Current Pharmaceutical Design Oncolytic Viruses: The Best is Yet to Come
Current Cancer Drug Targets Epigenetic Regulation of Trinucleotide Repeat Expansions and Contractions and the “Biased Embryos” Hypothesis for Rapid Morphological Evolution
Current Genomics Recent Advances in Optical Cancer Imaging of EGF Receptors
Current Medicinal Chemistry Lycopene: A Review of Its Potential as an Anticancer Agent
Current Medicinal Chemistry - Anti-Cancer Agents Lipid Metabolism and Relevant Disorders to Female Reproductive Health
Current Medicinal Chemistry Antineoplastic Activity of Monocrotaline Against Hepatocellular Carcinoma
Anti-Cancer Agents in Medicinal Chemistry Scope of Nanotechnology-based Radiation Therapy and Thermotherapy Methods in Cancer Treatment
Current Cancer Drug Targets Synthesis, Immunomodulation and Cytotoxic Effects of Vanadium (IV) Complexes
Medicinal Chemistry Synthesis and Pharmacological Effects of the Anti-Cancer Agent 2-Methoxyestradiol
Current Pharmaceutical Design