Targeting the Folate Receptor: Improving Efficacy in Inorganic 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.

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