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
-
The Cytoskeleton as a Therapeutic Target in Childhood Acute Leukemia:Obstacles and Opportunities
Current Drug Targets Novel Concepts in the Development of Platinum Antitumour Drugs: An Update
Medicinal Chemistry Reviews - Online (Discontinued) The Use of Fas Ligand, TRAIL and Bax in Gene Therapy of Prostate Cancer
Current Gene Therapy Defining and Managing Expectations for Early Immunotherapy Cancer Trials
Reviews on Recent Clinical Trials Hedgehog Signaling in the Normal and Neoplastic Mammary Gland
Current Drug Targets Time Dependent Distribution of MicroRNA 144 after Intravenous Delivery
MicroRNA Structure, Function, and Pathogenesis of SHP2 in Developmental Disorders and Tumorigenesis
Current Cancer Drug Targets Cucurbitacin E, An Experimental Lead Triterpenoid with Anticancer, Immunomodulatory and Novel Effects Against Degenerative Diseases. A Mini-Review
Current Topics in Medicinal Chemistry Stem Cell Differentiation Stage Factors and their Role in Triggering Symmetry Breaking Processes during Cancer Development: A Quantum Field Theory Model for Reprogramming Cancer Cells to Healthy Phenotypes
Current Medicinal Chemistry Plant Extracts and their Secondary Metabolites as Modulators of Kinases
Current Topics in Medicinal Chemistry Circulatory Estrogen Level Protects Against Breast Cancer in Obese Women
Recent Patents on Anti-Cancer Drug Discovery Essential Role of Gli Proteins in Glioblastoma Multiforme
Current Protein & Peptide Science Advances in Targeting Insulin-like Growth Factor Signaling Pathway in Cancer Treatment
Current Pharmaceutical Design Novel Insights Into c-Src
Current Pharmaceutical Design Susceptibility Risk Alleles of -238G/A, -308G/A and -1031T/C Promoter Polymorphisms of TNF-α Gene to Uterine Leiomyomas
Recent Advances in DNA & Gene Sequences (Discontinued) Status of Non-Classical Mononuclear Platinum Anticancer Drug Development
Mini-Reviews in Medicinal Chemistry Anti-VEGF Anticancer Drugs: Mind the Hypertension
Recent Advances in Cardiovascular Drug Discovery (Discontinued) Antiangiogenic Therapy for High-Grade Gliomas
CNS & Neurological Disorders - Drug Targets Recent Advances in Substrate Identification of Protein Kinases in Plants and Their Role in Stress Management
Current Genomics Case Report of a Large Rhinolith Cast – A Frequently Missed Diagnosis
New Emirates Medical Journal