Abstract
A novel trinuclear platinum compound with a cis-geometry for terminal metal centres coded as QH1 has been synthesized, characterized and investigated for activity against the human ovarian A2780, A2780cisR and A2780ZD0473R cancer cell lines. The cellular accumulation of platinum, level of platinum-DNA binding and the nature of interaction of the compound with pBR322 plasmid DNA have also been determined. QH1 is found to be more active against the resistant cell lines than the parent cell line, thus indicating that the compound has been able to overcome mechanisms of resistance operating in the A2780cisR and A2780ZD0473R cell lines. The high activity of QH1 is associated with high platinum accumulation and high level of platinum-DNA binding in all the three ovarian cancer cell lines. Provided QH1 has the right toxicity profile and its in vitro activity is matched with sufficient activity in vivo, the compound has the potential for development as a novel platinum-based anticancer drug targeted to the ovarian cancer.
Keywords: Ovarian cancer, A2780, cisplatin, drug resistance, multicentred platinum, pBR322 plasmid DNA, spectrum, trinuclear, detoxication, degradation
Medicinal Chemistry
Title:Synthesis and Activity of [{Cis-PtCl(NH3)2}2µ{Trans-Pt(3-Hydroxypyridine)2(H2N(CH2)6NH2)2}]Cl4 in the Human Ovarian Tumour Models.
Volume: 8 Issue: 3
Author(s): Shahnaz AH Hamad, Philip Beale, Jun Qing Yu, Keith Fisher and Fazlul Huq
Affiliation:
Keywords: Ovarian cancer, A2780, cisplatin, drug resistance, multicentred platinum, pBR322 plasmid DNA, spectrum, trinuclear, detoxication, degradation
Abstract: A novel trinuclear platinum compound with a cis-geometry for terminal metal centres coded as QH1 has been synthesized, characterized and investigated for activity against the human ovarian A2780, A2780cisR and A2780ZD0473R cancer cell lines. The cellular accumulation of platinum, level of platinum-DNA binding and the nature of interaction of the compound with pBR322 plasmid DNA have also been determined. QH1 is found to be more active against the resistant cell lines than the parent cell line, thus indicating that the compound has been able to overcome mechanisms of resistance operating in the A2780cisR and A2780ZD0473R cell lines. The high activity of QH1 is associated with high platinum accumulation and high level of platinum-DNA binding in all the three ovarian cancer cell lines. Provided QH1 has the right toxicity profile and its in vitro activity is matched with sufficient activity in vivo, the compound has the potential for development as a novel platinum-based anticancer drug targeted to the ovarian cancer.
Export Options
About this article
Cite this article as:
AH Hamad Shahnaz, Beale Philip, Qing Yu Jun, Fisher Keith and Huq Fazlul, Synthesis and Activity of [{Cis-PtCl(NH3)2}2µ{Trans-Pt(3-Hydroxypyridine)2(H2N(CH2)6NH2)2}]Cl4 in the Human Ovarian Tumour Models., Medicinal Chemistry 2012; 8 (3) . https://dx.doi.org/10.2174/157340612800786642
DOI https://dx.doi.org/10.2174/157340612800786642 |
Print ISSN 1573-4064 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6638 |
Call for Papers in Thematic Issues
Carbohydrates in Computational and Medicinal Chemistry
Carbohydrates are the most essential organic molecules and are involved in the maintenance of various physiological and metabolic processes in living organisms. Carbohydrate-based compounds have come to the attention of researchers because of their significant contributions to biological functions, such as cell development and cell proliferation, connections between several cells, ...read more
Recent Advances in the Medicinal Chemistry of Cancer
Scope of the Thematic Issue: Correlation between structure and function is one of the important aspects of the success of anti-cancer compounds associated with their structure-activity interactions, physiology, biochemical, molecular, and genetic processes. Overcoming these obstacles is key to obtaining further insights into developments in rational drug design, bioorganic chemistry, ...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
-
A Comprehensive Review of the Genus Pyrola Herbs in Traditional Uses, Phytochemistry and Pharmacological Activities
Current Topics in Medicinal Chemistry Macrophages in Immunopathology of Atherosclerosis: A Target for Diagnostics and Therapy
Current Pharmaceutical Design Antimetastatic Activities and Mechanisms of Bisdioxopiperazine Compounds
Anti-Cancer Agents in Medicinal Chemistry Regulation of HIPK Proteins by MicroRNAs
MicroRNA Diffusion-Weighted Imaging in Abdominal Oncology
Current Medical Imaging Drugs of Abuse: Epigenetic Mechanisms in Toxicity and Addiction
Current Medicinal Chemistry Non-histone Methylation of SET7/9 and its Biological Functions
Recent Patents on Anti-Cancer Drug Discovery Biologically Active Selenophenes and Benzo[b]selenophenes
Current Organic Synthesis Antiangiogenic Therapy and Ovarian Cancer
Current Women`s Health Reviews Non-Analgesic Effects of Opioids: The Interaction of Opioids with Bone and Joints
Current Pharmaceutical Design Physical Activity and Cancer Prevention: Updating the Evidence. The Role of Oxidative Stress in Carcinogenesis
Current Cancer Therapy Reviews Recent Patents on Thiazole Derivatives Endowed with Antitumor Activity
Recent Patents on Anti-Cancer Drug Discovery Progress in Topical siRNA Delivery Approaches for Skin Disorders
Current Pharmaceutical Design Nitric Oxide and the Regulation of Apoptosis in Tumour Cells
Current Pharmaceutical Design MicroRNA as Regulators of Cancer Stem Cells and Chemoresistance in Colorectal Cancer
Current Cancer Drug Targets Commercial Availability of Alpha-Emitting Radionuclides for Medicine
Current Radiopharmaceuticals The Retinoblastoma Protein in Osteoblast Differentiation and Osteosarcoma
Current Molecular Medicine Mesenchymal Stem Cells Derived from Wharton's Jelly of the Umbilical Cord: Biological Properties and Emerging Clinical Applications
Current Stem Cell Research & Therapy The Role of Bone Density Measurements in the Evaluation of New Treatments for Osteoporosis
Current Pharmaceutical Design Xanthohumol, a Prenylated Chalcone Derived from Hops, Suppresses Cancer Cell Invasion through Inhibiting the Expression of CXCR4 Chemokine Receptor
Current Molecular Medicine