Abstract
The metal-based drugs have gained increasing attention in the fight against cancer. Ga(III) in the form of inorganic salts has demonstrated efficacy in the treatment of a number of malignancies in experimental animals and humans, and has therefore attracted considerable pharmaceutical interest. However, the poor hydrolytic stability of Ga(III) in physiological medium owing to its property of hard Lewis acid prevents its widespread use in systemic cancer chemotherapy. Complexation of suitable chelators capable of stabilising Ga(III) against hydrolysis affords an opportunity for overcoming this drawback. Thiosemicarbazone (TSC) derivatives, a class of well-studied iron chelators featuring softer donor sulfur, also were evaluated to possess antineoplastic activities in an arrary of tumour cell lines. The structural modifications can affect the activities of TSCs, and related structure-activity relationships (SAR) have been studied over these years. Combination of Ga(III) and TSCs that are both pharmaceutically active has proved to exert synergistic effects of each component in one compound in most cases, and may produce more potent Ga(III) drugs. In this review, the SAR of α(N)-heterocyclic thiosemicarbazone (HCT) analogues, a family of TSCs, were scrupulously surveyed, and the effect of Ga(III) complexation on their anticancer activity sparsely reported in literature was comparatively examined, in order to stimulate further advances in the field of gallium-based anticancer drugs.
Keywords: Gallium, anticancer activity, sulfur-containing chelator, thiosemicarbazone, structure-activity relationships, complexation effect.
Anti-Cancer Agents in Medicinal Chemistry
Title:α(N)-Heterocyclic Thiosemicarbazones: Iron Chelators that are Promising for Revival of Gallium in Cancer Chemotherapy
Volume: 16 Issue: 8
Author(s): Shuhong Cao, Xiahui Chen, Ligen Chen and Jingwen Chen
Affiliation:
Keywords: Gallium, anticancer activity, sulfur-containing chelator, thiosemicarbazone, structure-activity relationships, complexation effect.
Abstract: The metal-based drugs have gained increasing attention in the fight against cancer. Ga(III) in the form of inorganic salts has demonstrated efficacy in the treatment of a number of malignancies in experimental animals and humans, and has therefore attracted considerable pharmaceutical interest. However, the poor hydrolytic stability of Ga(III) in physiological medium owing to its property of hard Lewis acid prevents its widespread use in systemic cancer chemotherapy. Complexation of suitable chelators capable of stabilising Ga(III) against hydrolysis affords an opportunity for overcoming this drawback. Thiosemicarbazone (TSC) derivatives, a class of well-studied iron chelators featuring softer donor sulfur, also were evaluated to possess antineoplastic activities in an arrary of tumour cell lines. The structural modifications can affect the activities of TSCs, and related structure-activity relationships (SAR) have been studied over these years. Combination of Ga(III) and TSCs that are both pharmaceutically active has proved to exert synergistic effects of each component in one compound in most cases, and may produce more potent Ga(III) drugs. In this review, the SAR of α(N)-heterocyclic thiosemicarbazone (HCT) analogues, a family of TSCs, were scrupulously surveyed, and the effect of Ga(III) complexation on their anticancer activity sparsely reported in literature was comparatively examined, in order to stimulate further advances in the field of gallium-based anticancer drugs.
Export Options
About this article
Cite this article as:
Cao Shuhong, Chen Xiahui, Chen Ligen and Chen Jingwen, α(N)-Heterocyclic Thiosemicarbazones: Iron Chelators that are Promising for Revival of Gallium in Cancer Chemotherapy, Anti-Cancer Agents in Medicinal Chemistry 2016; 16 (8) . https://dx.doi.org/10.2174/1871520616666160310142012
DOI https://dx.doi.org/10.2174/1871520616666160310142012 |
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
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
-
Hypoxia Responsive Drug Delivery Systems in Tumor Therapy
Current Pharmaceutical Design Current Status of Primary Cytoreductive Surgery for the Treatment of Advanced Epithelial Ovarian Cancer
Current Cancer Therapy Reviews Galectins: Major Signaling Modulators Inside and Outside the Cell
Current Molecular Medicine The Pim Kinases: New Targets for Drug Development
Current Drug Targets Anti-Inflammatory Drugs and Prediction of New Structures by Comparative Analysis
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Stimulation of Peroxisome Proliferator-Activated Receptor-Gamma (PPARγ) using Pioglitazone Decreases the Survival of Acute Promyelocytic Leukemia Cells through Up-Regulation of PTEN Expression
Anti-Cancer Agents in Medicinal Chemistry Botulinum Toxin: Pharmacology and Clinical Developments: A Literature Review
Medicinal Chemistry Metabolic Cooperation in Testis as a Pharmacological Target: From Disease to Contraception
Current Molecular Pharmacology Editorial (Thematic Issue: Endothelium: A Target for Therapeutic Intervention)
Current Vascular Pharmacology Molecular Targeted Approaches to Cancer Therapy and Prevention Using Chalcones
Current Cancer Drug Targets Cancer Estimates in Brazil Reveal Progress for the Most Lethal Malignancies
Current Topics in Medicinal Chemistry A Novel Polyarginine Containing Smac Peptide Conjugate that Mediates Cell Death in Tumor and Healthy Cells
Medicinal Chemistry Regulation of Multidrug Resistance by Pro-Inflammatory Cytokines
Current Cancer Drug Targets Cellular Iron Homeostasis and Therapeutic Implications of Iron Chelators in Cancer
Current Pharmaceutical Biotechnology Antioxidant Supplementation on Cancer Risk and During Cancer Therapy: An Update
Current Topics in Medicinal Chemistry Recent Advances in Receptor-Targeted Fluorescent Probes for In Vivo Cancer Imaging
Current Medicinal Chemistry Post-Translational Protein Modifications of Rare and Unconventional Types: Implications in Functions and Diseases
Current Medicinal Chemistry The Roles of Histone Demethylase UTX and JMJD3 (KDM6B) in Cancers: Current Progress and Future Perspectives
Current Medicinal Chemistry Manganese Superoxide Dismutase (Sod2) and Redox-Control of Signaling Events That Drive Metastasis
Anti-Cancer Agents in Medicinal Chemistry Biology and Therapeutic Applications of Peroxisome Proliferator- Activated Receptors
Current Topics in Medicinal Chemistry