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
- 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
-
Evolution of the DUT Gene: Horizontal Transfer between Host and Pathogen in all Three Domains of Life
Current Protein & Peptide Science Pharmacologic Role of Vitamin D Natural Products
Current Vascular Pharmacology Design, Synthesis and Computational Studies of New Benzothiazole Substituted Quinazolines as Potential Antimicrobial Agents
Letters in Drug Design & Discovery Pleural Involvement in Systemic Disorders
Current Drug Targets - Inflammation & Allergy The Manzamines as an Example of the Unique Structural Classes Available for the Discovery and Optimization of Infectious Disease Controls Based on Marine Natural Products
Current Pharmaceutical Design Unequivocal Role of Pyrazine Ring in Medicinally Important Compounds: A Review
Mini-Reviews in Medicinal Chemistry Phage Choice, Isolation, and Preparation for Phage Therapy
Current Pharmaceutical Biotechnology An Overview of Currently Available Antimalarials
Current Topics in Medicinal Chemistry Recent Patents on Immunoregulatory DNA Vaccines for Autoimmune Diseases and Allograft Rejection
Recent Patents on DNA & Gene Sequences Molecular Delivery of Plasmids for Genetic Vaccination
Current Pharmaceutical Biotechnology Recent Developments of Thalidomide Derivatives Possessing Anti-Inflammatory Activity
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Cloning, Expression and Correlation of Rv0148 to Amikacin & Kanamycin Resistance
Current Proteomics A Simple and Green Procedure for the Synthesis of N-Benzylthioureas
Letters in Organic Chemistry Syphilis: An Epidemiological Review
Current Women`s Health Reviews Current Studies of Osteoclastogenesis and Potential Drug Targets
Current Drug Targets Novel Urea/Thiourea Derivatives of Quinazolin-4(3H)-one: Design, Synthesis, Antimicrobial and Anti-TB Study
Letters in Drug Design & Discovery Anti-Inflammatory Trends of 1, 3-Diphenyl-2-propen-1-one Derivatives
Mini-Reviews in Medicinal Chemistry A Review of the Computational Methods for Identifying the Over- Annotated Genes and Missing Genes in Microbial Genomes
Current Bioinformatics Lipid-Specific Immune Responses Against Tuberculosis: From Basic Science to Medical Applications
Current Immunology Reviews (Discontinued) Recent Advances in Tuberculosis Vaccine Development
Current Respiratory Medicine Reviews