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Water solubility enhancement of pyrazolo[3,4-d]pyrimidine derivatives via miniaturized polymer-drug microarrays

Sanna, Monica; Sicilia, Giovanna; Alazzo, Ali; Singh, Nishant; Musumeci, Francesca; Schenone, Silvia; Spriggs, Keith; Burley, Jonathan C.; Garnett, Martin; Taresco, Vincenzo; Alexander, Cameron

Authors

Monica Sanna

Giovanna Sicilia

Ali Alazzo Ali.Alazzo@nottingham.ac.uk

Nishant Singh

Francesca Musumeci

Silvia Schenone

Martin Garnett martin.garnett@nottingham.ac.uk



Abstract

A miniaturized assay was optimized to evaluate the enhanced apparent water solubility of pyrazolo[3,4-d]pyrimidine derivatives used extensively as anticancer drug scaffolds. The applied amount of drugs used in the reported strategy ranged from 5-10 μg per formulation which were dispensed by an inkjet 2D printer directly into a 96-well plate. The selected polymer/drug formulations with high water solubility demonstrated improved cytotoxicity against a human lung adenocarcinoma cancer cell line (A549) compared to the free drugs. We attribute the enhanced efficacy to the improved apparent-solubility of the drug molecules achieved via this methodology. This novel miniaturized method showed promising results in terms of water solubility improvement of the highly hydrophobic pyrazolo[3,4-d]pyrimidine derivatives, requiring only a few μg of each drug per tested polymeric formulation. In addition, the reported experimental evidence may facilitate identification of suitable polymers for combination with drug leading to investigations on biological properties or mechanisms of action in a single formulation.

Citation

Sanna, M., Sicilia, G., Alazzo, A., Singh, N., Musumeci, F., Schenone, S., …Alexander, C. (in press). Water solubility enhancement of pyrazolo[3,4-d]pyrimidine derivatives via miniaturized polymer-drug microarrays. ACS Medicinal Chemistry Letters, 9(3), https://doi.org/10.1021/acsmedchemlett.7b00456

Journal Article Type Article
Acceptance Date Jan 29, 2018
Online Publication Date Jan 29, 2018
Deposit Date Feb 1, 2018
Publicly Available Date Jan 30, 2019
Journal ACS Medicinal Chemistry Letters
Print ISSN 1948-5875
Electronic ISSN 1948-5875
Publisher American Chemical Society
Peer Reviewed Peer Reviewed
Volume 9
Issue 3
DOI https://doi.org/10.1021/acsmedchemlett.7b00456
Keywords Miniaturized assay; inkjet 2D printing; amorphous solid dispersion; water solubility enhancement and pyrazolo[
3,4-d]pyrimidines
Public URL http://eprints.nottingham.ac.uk/id/eprint/49478
Publisher URL http://pubs.acs.org/doi/10.1021/acsmedchemlett.7b00456
Copyright Statement Copyright information regarding this work can be found at the following address: http://eprints.nottingham.ac.uk/end_user_agreement.pdf
Additional Information This document is the Accepted Manuscript version of a Published Work that appeared in final form in ACS Medicinal Chemistry Letters, copyright © American Chemical Society
after peer review and technical editing by the publisher.
To access the final edited and published work see https://doi.org/10.1021/acsmedchemlett.7b00456

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Copyright Statement
Copyright information regarding this work can be found at the following address: http://eprints.nottingham.ac.uk/end_user_agreement.pdf





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