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
-
Attenuation of ERK/RSK2-Driven NFκB Gene Expression and Cancer Cell Proliferation by Kurarinone, a Lavandulyl Flavanone Isolated from Sophora flavescens Ait. Roots
Endocrine, Metabolic & Immune Disorders - Drug Targets Targeted Drug Delivery to Macrophages in Parasitic Infections
Current Drug Delivery Bio-analytical Identification of Key Genes that Could Contribute to the Progression and Metastasis of Osteosarcoma
Current Bioinformatics Adenovirus As An Integrating Vector
Current Gene Therapy The Human L1 Element: A Potential Biomarker in Cancer Prognosis, Current Status and Future Directions
Current Molecular Medicine Induced Pluripotent Stem Cell Technology: A Paradigm Shift in Medical Science for Drug Screening and Disease Modeling
Current Medicinal Chemistry Curcumin and its Formulations: Potential Anti-Cancer Agents
Anti-Cancer Agents in Medicinal Chemistry Targeted Tumor Immunotherapy: Are Vaccines the Future of Cancer Treatment?
Current Drug Therapy Circumventing Immune Tolerance Through Epigenetic Modification
Current Pharmaceutical Design Postmenopausal Persistent Unilocular Ovarian Formations are not Risk Factor for Ovarian Carcinoma. A Long-Term Follow-Up Cohort Study
Current Women`s Health Reviews Drug Tissue Distribution: Study Methods and Therapeutic Implications
Current Pharmaceutical Design Pharmacological Modulation of Sphingolipids and Role in Disease and Cancer Cell Biology
Mini-Reviews in Medicinal Chemistry PI3K Pathway Inhibitors: Better Not Left Alone
Current Pharmaceutical Design Insights into Targeting Colon Cancer Cell Fate at the Level of Proteoglycans / Glycosaminoglycans
Current Medicinal Chemistry Metallothionein as a Scavenger of Free Radicals - New Cardioprotective Therapeutic Agent or Initiator of Tumor Chemoresistance?
Current Drug Targets 2-(2-Arylidenehydrazinyl) Thiazol-4(5H)-ones as Epidermal Growth Factor Receptor Inhibitors: A Combined Quantitative Structure Activity Relationship and Pharmacophore Study
Current Enzyme Inhibition Targeting the BH3 Domain of Bcl-2 Family Proteins. A Brief History From Natural Products to Foldamers As Promising Cancer Therapeutic Avenues
Current Medicinal Chemistry Breastfeeding and Diabetes
Current Diabetes Reviews Aldose Reductase Inhibitor, Fidarestat Prevents High-fat Diet-induced Intestinal Polyps in ApcMin/+ Mice
Current Cancer Drug Targets p53 Peptide Prevents LITAF-Induced TNF-Alpha-Mediated Mouse Lung Lesions and Endotoxic Shock
Current Molecular Medicine