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

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 inkje...

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Main Authors: Sanna, Monica, Sicilia, Giovanna, Alazzo, Ali, Singh, Nishant, Musumeci, Francesca, Schenone, Silvia, Spriggs, Keith, Burley, Jonathan C., Garnett, Martin, Taresco, Vincenzo, Alexander, Cameron
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Published: American Chemical Society 2018
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Online Access:https://eprints.nottingham.ac.uk/49478/
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author Sanna, Monica
Sicilia, Giovanna
Alazzo, Ali
Singh, Nishant
Musumeci, Francesca
Schenone, Silvia
Spriggs, Keith
Burley, Jonathan C.
Garnett, Martin
Taresco, Vincenzo
Alexander, Cameron
author_facet Sanna, Monica
Sicilia, Giovanna
Alazzo, Ali
Singh, Nishant
Musumeci, Francesca
Schenone, Silvia
Spriggs, Keith
Burley, Jonathan C.
Garnett, Martin
Taresco, Vincenzo
Alexander, Cameron
author_sort Sanna, Monica
building Nottingham Research Data Repository
collection Online Access
description 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.
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publishDate 2018
publisher American Chemical Society
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spelling nottingham-494782020-05-04T19:28:36Z https://eprints.nottingham.ac.uk/49478/ 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 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. American Chemical Society 2018-01-29 Article PeerReviewed Sanna, Monica, Sicilia, Giovanna, Alazzo, Ali, Singh, Nishant, Musumeci, Francesca, Schenone, Silvia, Spriggs, Keith, Burley, Jonathan C., Garnett, Martin, Taresco, Vincenzo and Alexander, Cameron (2018) Water solubility enhancement of pyrazolo[3,4-d]pyrimidine derivatives via miniaturized polymer-drug microarrays. ACS Medicinal Chemistry Letters, 9 (3). pp. 193-197. ISSN 1948-5875 Miniaturized assay; inkjet 2D printing; amorphous solid dispersion; water solubility enhancement and pyrazolo[ 3 4-d]pyrimidines http://pubs.acs.org/doi/10.1021/acsmedchemlett.7b00456 doi:10.1021/acsmedchemlett.7b00456 doi:10.1021/acsmedchemlett.7b00456
spellingShingle Miniaturized assay; inkjet 2D printing; amorphous solid dispersion; water solubility enhancement and pyrazolo[ 3
4-d]pyrimidines
Sanna, Monica
Sicilia, Giovanna
Alazzo, Ali
Singh, Nishant
Musumeci, Francesca
Schenone, Silvia
Spriggs, Keith
Burley, Jonathan C.
Garnett, Martin
Taresco, Vincenzo
Alexander, Cameron
Water solubility enhancement of pyrazolo[3,4-d]pyrimidine derivatives via miniaturized polymer-drug microarrays
title Water solubility enhancement of pyrazolo[3,4-d]pyrimidine derivatives via miniaturized polymer-drug microarrays
title_full Water solubility enhancement of pyrazolo[3,4-d]pyrimidine derivatives via miniaturized polymer-drug microarrays
title_fullStr Water solubility enhancement of pyrazolo[3,4-d]pyrimidine derivatives via miniaturized polymer-drug microarrays
title_full_unstemmed Water solubility enhancement of pyrazolo[3,4-d]pyrimidine derivatives via miniaturized polymer-drug microarrays
title_short Water solubility enhancement of pyrazolo[3,4-d]pyrimidine derivatives via miniaturized polymer-drug microarrays
title_sort water solubility enhancement of pyrazolo[3,4-d]pyrimidine derivatives via miniaturized polymer-drug microarrays
topic Miniaturized assay; inkjet 2D printing; amorphous solid dispersion; water solubility enhancement and pyrazolo[ 3
4-d]pyrimidines
url https://eprints.nottingham.ac.uk/49478/
https://eprints.nottingham.ac.uk/49478/
https://eprints.nottingham.ac.uk/49478/