Abstract
The ideal drug discovery process of new platinum based drugs should take into account three basic fundaments: on one side the mechanisms of action and the corresponding target biomolecules, on the other side, the possible mechanisms of resistance of cancer cells and their biochemical pathways and, finally, the pharmacokinetic and toxicity properties (ADMET) that will condition the clinical usefulness of the new drugs. At the end of this rational process always we face the necessity to design a molecule with a structure and certain physical and chemical properties. The structure is then a key fundamental issue when thinking of new anticancer platinum compounds. When analyzing the influence of molecular structure on anticancer activity it is useful to make the dissection of platinum complexes into different significant subunits or moieties, of the molecular structure. Thus, the following structural and electron dependent parameters are important to facilitate the comparison among platinum complexes: a) Nature of the non-labile ligand or carrier ligand (NLG); b) Nature of the labile ligand or leaving group (LG); c) Oxidation state of platinum atom; d) Type of atoms (connecting atoms X, Y, Z, W) that link ligands to platinum atom; e) Nature of the axial groups (AG) in platinum(IV) complexes; f) Nuclearity or number of Pt atoms in the platinum complexes; g) Formal charges present in the molecule and h) Intrinsic bioactivity of some ligands or bioactivity induced by molecules attached to ligands by linkers (in order to get a double mechanism of action or a parallel biological activity).
Keywords: Platinum complexes, anticancer agents, SAR (structure-activity relationship), rational drug design
Current Medicinal Chemistry
Title: The Rational Design of Anticancer Platinum Complexes: The Importance of the Structure-Activity Relationship
Volume: 16 Issue: 18
Author(s): Angel M. Montana and Consuelo Batalla
Affiliation:
Keywords: Platinum complexes, anticancer agents, SAR (structure-activity relationship), rational drug design
Abstract: The ideal drug discovery process of new platinum based drugs should take into account three basic fundaments: on one side the mechanisms of action and the corresponding target biomolecules, on the other side, the possible mechanisms of resistance of cancer cells and their biochemical pathways and, finally, the pharmacokinetic and toxicity properties (ADMET) that will condition the clinical usefulness of the new drugs. At the end of this rational process always we face the necessity to design a molecule with a structure and certain physical and chemical properties. The structure is then a key fundamental issue when thinking of new anticancer platinum compounds. When analyzing the influence of molecular structure on anticancer activity it is useful to make the dissection of platinum complexes into different significant subunits or moieties, of the molecular structure. Thus, the following structural and electron dependent parameters are important to facilitate the comparison among platinum complexes: a) Nature of the non-labile ligand or carrier ligand (NLG); b) Nature of the labile ligand or leaving group (LG); c) Oxidation state of platinum atom; d) Type of atoms (connecting atoms X, Y, Z, W) that link ligands to platinum atom; e) Nature of the axial groups (AG) in platinum(IV) complexes; f) Nuclearity or number of Pt atoms in the platinum complexes; g) Formal charges present in the molecule and h) Intrinsic bioactivity of some ligands or bioactivity induced by molecules attached to ligands by linkers (in order to get a double mechanism of action or a parallel biological activity).
Export Options
About this article
Cite this article as:
Montana M. Angel and Batalla Consuelo, The Rational Design of Anticancer Platinum Complexes: The Importance of the Structure-Activity Relationship, Current Medicinal Chemistry 2009; 16 (18) . https://dx.doi.org/10.2174/092986709788453087
DOI https://dx.doi.org/10.2174/092986709788453087 |
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
-
Animal Mitochondria: Evolution, Function, and Disease
Current Molecular Medicine Metabolic Targeting of Cancers: From Molecular Mechanisms to Therapeutic Strategies
Current Medicinal Chemistry Naturally Occurring Hydroxytyrosol: Synthesis and Anticancer Potential
Current Medicinal Chemistry Inhibitors of Nitrogen Oxide Species Production in Animal Models of Inflammation and Future Directions for Therapy in Inflammatory Disorders
Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents The HOX Gene Network as a Potential Target for Cancer Therapy
Current Cancer Therapy Reviews Zoledronic Acid -a Multiplicity of Anti-Cancer Action
Current Medicinal Chemistry Triterpenoids for Cancer Prevention and Treatment: Current Status and Future Prospects
Current Pharmaceutical Biotechnology Angiotensin II Receptor Blocker: Possibility of Antitumor Agent for Prostate Cancer
Mini-Reviews in Medicinal Chemistry General Theory for Multiple Input-Output Perturbations in Complex Molecular Systems. 1. Linear QSPR Electronegativity Models in Physical, Organic, and Medicinal Chemistry
Current Topics in Medicinal Chemistry Aldehyde Dehydrogenase as a Marker for Stem Cells
Current Stem Cell Research & Therapy Isoniazid: Metabolic Aspects and Toxicological Correlates
Current Drug Metabolism In Vitro Regulatory Effect of Epididymal Serpin CRES on Protease Activity of Proprotein Convertase PC4/PCSK4
Current Molecular Medicine Efficacy and Safety of Nonopioid Analgesics in Perioperative Pain Control
Current Drug Safety Update of the Preclinical Situation of Anticancer Platinum Complexes: Novel Design Strategies and Innovative Analytical Approaches
Current Medicinal Chemistry The Disulfide Analogues of Isophosphoramide Mustard for Anticancer Therapy
Letters in Drug Design & Discovery Viral Vectors for Gene-Directed Enzyme Prodrug Therapy
Current Gene Therapy Silibinin – A Promising New Treatment for Cancer
Anti-Cancer Agents in Medicinal Chemistry Aflibercept (VEGF-TRAP): The Next Anti-VEGF Drug
Inflammation & Allergy - Drug Targets (Discontinued) Cell Cycle as a Target of Antineoplastic Drugs
Current Pharmaceutical Design Curcumin: A Natural Product for Diabetes and its Complications
Current Topics in Medicinal Chemistry