Targeting the folate receptor: Improving efficacy in inorganic medicinal chemistry

Authors

Pauraic McCarron, Technological University DublinFollow
Aisling Crowley, Technological University DublinFollow
Denis O'Shea, Technological University DublinFollow
Malachy McCann, National University of Ireland, Maynooth
Orla L. Howe, Technological University DublinFollow
Mary Hunt, Technological University DublinFollow
Michael Devereux, Technological University DublinFollow

Document Type

Article

Rights

Available under a Creative Commons Attribution Non-Commercial Share Alike 4.0 International Licence

Disciplines

1.4 CHEMICAL SCIENCES, 3. MEDICAL AND HEALTH SCIENCES

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.

DOI

http://dx.doi.org/10.2174/0929867325666180209143715

Recommended Citation

Mc Carron, Pauraic & Crowley, Aisling & Shea, Denis & Mccann, Malachy & Howe, Orla & Hunt, Mary & Devereux, Michael. (2018). Targeting the Folate Receptor: Improving Efficacy in Inorganic Medicinal Chemistry. Current Medicinal Chemistry. 25. 10.2174/0929867325666180209143715.