Abstract
The research of new platinum drugs active towards cisplatin refractory/resistant tumors has been mostly focussed on compounds with cis geometry because transplatin, the trans-isomer of cisplatin, is inactive. It is widely accepted that transplatin inactivity stems from two major factors: i) the kinetic instability promoting its deactivation and ii) the formation of DNA adducts characterized by a regioselectivity and a stereochemistry different from those of cisplatin. However, several exceptions to the general rule that the presence of two leaving groups in cis positions is necessary for antitumor activity of platinum complexes, have been reported. Substitution of transplatin ammine ligands by aromatic Ndonor heterocycles, branched aliphatic amines, or imino ligands has lead to compounds with relevant in vitro tumor cell growth inhibitory potency, often active towards cisplatin refractory/resistant tumor cells, and in some cases endowed with significant activity also in vivo. From a mechanistic point of view, substitution of bulky ligands for ammines can retard substitution of the two chloride ligands, thus reducing the kinetic instability of the trans-platinum compounds. On the other hand, the formation of DNA adducts qualitatively and quantitatively different from those of cisplatin strongly supports the hypothesis that antitumor-active trans-platinum complexes can have a different spectrum of activity. It is hoped that the increasing knowledge of the biochemical and cellular processes underlying the antitumor-activity of transplatinum complexes will foster their clinical development.
Keywords: Platinum antitumor drugs, breast cancer, trans configuration, DNA interaction, cell cycle perturbation, gene expression profiling
Anti-Cancer Agents in Medicinal Chemistry
Title: Trans-Platinum Complexes in Cancer Therapy
Volume: 7 Issue: 1
Author(s): Mauro Coluccia and Giovanni Natile
Affiliation:
Keywords: Platinum antitumor drugs, breast cancer, trans configuration, DNA interaction, cell cycle perturbation, gene expression profiling
Abstract: The research of new platinum drugs active towards cisplatin refractory/resistant tumors has been mostly focussed on compounds with cis geometry because transplatin, the trans-isomer of cisplatin, is inactive. It is widely accepted that transplatin inactivity stems from two major factors: i) the kinetic instability promoting its deactivation and ii) the formation of DNA adducts characterized by a regioselectivity and a stereochemistry different from those of cisplatin. However, several exceptions to the general rule that the presence of two leaving groups in cis positions is necessary for antitumor activity of platinum complexes, have been reported. Substitution of transplatin ammine ligands by aromatic Ndonor heterocycles, branched aliphatic amines, or imino ligands has lead to compounds with relevant in vitro tumor cell growth inhibitory potency, often active towards cisplatin refractory/resistant tumor cells, and in some cases endowed with significant activity also in vivo. From a mechanistic point of view, substitution of bulky ligands for ammines can retard substitution of the two chloride ligands, thus reducing the kinetic instability of the trans-platinum compounds. On the other hand, the formation of DNA adducts qualitatively and quantitatively different from those of cisplatin strongly supports the hypothesis that antitumor-active trans-platinum complexes can have a different spectrum of activity. It is hoped that the increasing knowledge of the biochemical and cellular processes underlying the antitumor-activity of transplatinum complexes will foster their clinical development.
Export Options
About this article
Cite this article as:
Coluccia Mauro and Natile Giovanni, Trans-Platinum Complexes in Cancer Therapy, Anti-Cancer Agents in Medicinal Chemistry 2007; 7 (1) . https://dx.doi.org/10.2174/187152007779314080
DOI https://dx.doi.org/10.2174/187152007779314080 |
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
-
Application of High Performance Liquid Chromatography for Hydrolytic Stability Assessment of Selected Antibiotics in Aqueous Environment
Current Analytical Chemistry Performance Identification Using Morphological Approach on Digital Mammographic Images
Current Signal Transduction Therapy Targeting Lipoxygenases (LOs): Drug Design And Discovery
Current Enzyme Inhibition Editorial (Thematic Issue: Targeting Anti-Cancer Agents and Cancer Treatments)
Anti-Cancer Agents in Medicinal Chemistry Recent Trends of Chalcones Potentialities as Antiproliferative and Antiresistance Agents
Anti-Cancer Agents in Medicinal Chemistry Ovarian Toxicity: From Environmental Exposure to Chemotherapy
Current Pharmaceutical Design In Vitro and In Vivo Biodistribution of ZRS1, a Stabilized Type I N-Acetoxymethyl Carbamate-Containing Combi-Molecule
Drug Metabolism Letters Bioinformatics Approaches to Profile the Tumor Microenvironment for Immunotherapeutic Discovery
Current Pharmaceutical Design Cancer Genetics and Drug Discovery in Mice
Letters in Drug Design & Discovery Applications of Peptide Mimetics in Cancer
Current Medicinal Chemistry Regulatory T Cells and Allergic Disease
Inflammation & Allergy - Drug Targets (Discontinued) Predictive Biomarkers to Tyrosine Kinase Inhibitors for the Epidermal Growth Factor Receptor in Non-Small-Cell Lung Cancer
Current Drug Targets The Synthesis of Nano-Doxorubicin and its Anticancer Effect
Anti-Cancer Agents in Medicinal Chemistry The ERK and p38MAPK Pathways as Targets for Anti-Inflammatory Therapy
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Strategies for Preparing Different Types of Lipid Polymer Hybrid Nanoparticles in Targeted Tumor Therapy
Current Pharmaceutical Design Influence of Polymer Molecular Weight on in-vitro Characteristics and Cytotoxicity of Fulvestrant Loaded Nanoparticles
Current Drug Therapy Synthetic Lethality: From Research to Precision Cancer Nanomedicine
Current Cancer Drug Targets Oral Nano-Delivery Systems for Colon Targeting Therapy
Pharmaceutical Nanotechnology Oleocanthal, a Natural anti-Inflammatory Compound in Extra Virgin Olive Oil
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Penetration of Tamoxifen Citrate Loaded Ethosomes and Liposomes Across Human Skin: A Comparative Study with Confocal Laser Scanning Microscopy
Current Drug Delivery