Abstract
The main aim of this study was to enhance the solubility of pyrazolo[3,4-d]pyrimidines 1-8 able to strongly inhibit Src and Abl tyrosine kinase phosphorylation in cell-free assays and to significantly reduce leukemic and osteosarcoma cell lines growth, but characterized by very low solubility in aqueous media. Their water solubility was improved between 100 and 1000 folds by solubilization with 2-hydroxypropyl-β-cyclodextrin (HPβCD) and ratio of inclusion complex were determined by phase solubility method. Finally, some complexed compounds were tested on different leukemic (K-652, KU-812 and HL-60) and osteosarcoma (SaOS-2) cell lines showing a good enhancement of biological response in comparison with the not complexed compounds.
Copyright © 2010 Elsevier Masson SAS. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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2-Hydroxypropyl-beta-cyclodextrin
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Antineoplastic Agents / chemical synthesis
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology*
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Cell Proliferation / drug effects
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Drug Screening Assays, Antitumor
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HL-60 Cells
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Humans
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Molecular Structure
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Protein Kinase Inhibitors / chemical synthesis
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Protein Kinase Inhibitors / chemistry
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Protein Kinase Inhibitors / pharmacology*
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Pyrazoles / chemical synthesis
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Pyrazoles / chemistry
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Pyrazoles / pharmacology*
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Pyrimidines / chemical synthesis
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Pyrimidines / chemistry
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Pyrimidines / pharmacology*
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Solubility
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Stereoisomerism
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Structure-Activity Relationship
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Tumor Cells, Cultured
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Water / chemistry
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beta-Cyclodextrins / chemistry*
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src-Family Kinases / antagonists & inhibitors*
Substances
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Antineoplastic Agents
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Protein Kinase Inhibitors
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Pyrazoles
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Pyrimidines
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beta-Cyclodextrins
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Water
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2-Hydroxypropyl-beta-cyclodextrin
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pyrazolo(3,4-d)pyrimidine
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src-Family Kinases