Abstract
The discovery of the high-affinity, high-specificity folate receptor in mamalian kidney cells, coupled with the ability of folate to enter cells by folate receptor-mediated endocytosis and the subsequent elucidation of the folate receptor’s overexpression in specific cancer cell types; heralded the arrival of the area of chemotherapeutic folate targeting. The application of purely organic folate-based small-molecule drug conjugates that selectively target the folate receptor, which is over expressed in several diseases such as cancer, is well established. The application of inorganic folate-targeted drugs offers significant potential to expand and enhance this therapeutic approach. From the data made available to date, it is apparent that this aspect of inorganic medicinal chemistry is in its youth but has the capability to contribute greatly to cancer research, both in therapy and diagnosis. The union of folate-receptor targeting and inorganic medicine may also lead to the development of treatments for disorders such as chronic-inflammation, tuberculosis, neurodegenerative disease and leishmaniasis. In this review, we summarize what is known about the coordination chemistry of folic acid and the therapeutic potential of such complexes. We also describe approaches adopted to conjugate platinum drugs to folate- or folate-carrier- systems and their prospective ability to overcome problems associated with unwanted side-effects and resistance by improving their delivery and/or selectivity. The literature pertaining to non-platinum metal complex conjugates with folic acid is also reviewed revealing that this is an area that offers significant potential to develop targeted therapeutic approaches in areas such as chemotherapy and molecular imaging for diagnostics.
Keywords: Metal-folate complexes, folate receptor-targeted drug delivery, chemotherapeutics, diagnostics, DHFR.
Current Medicinal Chemistry
Title:Targeting the Folate Receptor: Improving Efficacy in Inorganic Medicinal Chemistry
Volume: 25 Issue: 23
Author(s): Pauraic Mc Carron, Aisling Crowley, Denis O’Shea, Malachy McCann, Orla Howe, Mary Hunt and Michael Devereux*
Affiliation:
- The Centre for Biomimetic & Therapeutic Research, Focas Research Institute, Dublin Institute of Technology, Camden Row, Dublin 8,Ireland
Keywords: Metal-folate complexes, folate receptor-targeted drug delivery, chemotherapeutics, diagnostics, DHFR.
Abstract: The discovery of the high-affinity, high-specificity folate receptor in mamalian kidney cells, coupled with the ability of folate to enter cells by folate receptor-mediated endocytosis and the subsequent elucidation of the folate receptor’s overexpression in specific cancer cell types; heralded the arrival of the area of chemotherapeutic folate targeting. The application of purely organic folate-based small-molecule drug conjugates that selectively target the folate receptor, which is over expressed in several diseases such as cancer, is well established. The application of inorganic folate-targeted drugs offers significant potential to expand and enhance this therapeutic approach. From the data made available to date, it is apparent that this aspect of inorganic medicinal chemistry is in its youth but has the capability to contribute greatly to cancer research, both in therapy and diagnosis. The union of folate-receptor targeting and inorganic medicine may also lead to the development of treatments for disorders such as chronic-inflammation, tuberculosis, neurodegenerative disease and leishmaniasis. In this review, we summarize what is known about the coordination chemistry of folic acid and the therapeutic potential of such complexes. We also describe approaches adopted to conjugate platinum drugs to folate- or folate-carrier- systems and their prospective ability to overcome problems associated with unwanted side-effects and resistance by improving their delivery and/or selectivity. The literature pertaining to non-platinum metal complex conjugates with folic acid is also reviewed revealing that this is an area that offers significant potential to develop targeted therapeutic approaches in areas such as chemotherapy and molecular imaging for diagnostics.
Export Options
About this article
Cite this article as:
Carron Mc Pauraic, Crowley Aisling , O’Shea Denis , McCann Malachy, Howe Orla , Hunt Mary and Devereux Michael *, Targeting the Folate Receptor: Improving Efficacy in Inorganic Medicinal Chemistry, Current Medicinal Chemistry 2018; 25 (23) . https://dx.doi.org/10.2174/0929867325666180209143715
DOI https://dx.doi.org/10.2174/0929867325666180209143715 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
![](/images/wayfinder.jpg)
- 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
- Announcements
Related Articles
-
2', 4'-dihydroxy-3, 4-methylenedioxychalcone Activate Mitochondrial Apoptosis of Ehrlich Ascites Carcinoma Cells
Current Drug Therapy Adherence to Antiretroviral Therapy Among Iranian HIV/AIDS Patients
Current Clinical Pharmacology Chromenopyridines: Promising Scaffolds for Medicinal and Biological Chemistry
Current Medicinal Chemistry Synthesis and Molecular Docking Studies of Glucose-linked Isonicotinoyl- 1,3,4-Thiadiazolidines as Antitubercular Agents
Letters in Organic Chemistry Therapeutic Use of Antioxidants in Sepsis
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery (Discontinued) Antimicrobial peptides for the treatment of pulmonary tuberculosis, allies or foes?
Current Pharmaceutical Design Gaultheria Ethnobotany and Bioactivity: Blueberry Relatives with Anti-inflammatory, Antioxidant, and Anticancer Constituents
Current Medicinal Chemistry Rationalizing the Study of Plants for the Treatment of Oral Pain
Current Chemical Biology From Mice to Macaques – Animal Models of HIV Nervous System Disease
Current HIV Research Current Insights into the Chemistry and Antitubercular Potential of Benzimidazole and Imidazole Derivatives
Mini-Reviews in Medicinal Chemistry Key Amino Acids of Arabidopsis VKOR in the Activity of Phylloquinone Reduction and Disulfide Bond Formation
Protein & Peptide Letters Efficacy of Bacteria in Cancer Immunotherapy: Special Emphasis on the Potential of Mycobacterial Species
Clinical Cancer Drugs Immunomodulatory and Anti-inflammatory Properties of Artesunate in Experimental Colitis
Current Medicinal Chemistry Pathophysiology, Current Therapeutic Options, Vaccine Candidates, and Drug Targets for Human Brucellosis
Current Molecular Pharmacology 4-Mer Hyaluronan Oligosaccharides Stimulate Inflammation Response in Synovial Fibroblasts in Part via TAK-1 and in Part via p38-MAPK
Current Medicinal Chemistry Self-assembled Antibiotic Nanoparticles Against Intracellular Bacteria
Drug Delivery Letters New Analogues of Mycophenolic Acid
Mini-Reviews in Medicinal Chemistry The Application of High Throughput siRNA Screening Technology to Study Host-Pathogen Interactions
Combinatorial Chemistry & High Throughput Screening The Multifaceted Roles of Molecular Dynamics Simulations in Drug Discovery
Current Pharmaceutical Design Bioactive Compounds Containing Benzoxadiazole, Benzothiadiazole, Benzotriazole
Current Bioactive Compounds