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

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., Spriggs, K., Burley, J. C., Garnett, M., Taresco, V., & 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
• 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: https://nottingham-repository.worktribe.com/output/907262
• Publisher URL: http://pubs.acs.org/doi/10.1021/acsmedchemlett.7b00456
• 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
• Contract Date: Feb 1, 2018