2-Hydroxypropyl-β-cyclodextrin strongly improves water solubility and anti-proliferative activity of pyrazolo[3,4-d]pyrimidines Src-Abl dual inhibitors
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- 作者：Elena Dreassi ; Aless ; ra Tania Zizzari ; Mattia Mori ; Irene Filippi ; Amalia Belfiore ; Antonella Naldini ; Fabio Carraro ; Annalisa Santucci ; Silvia Schenone ; Maurizio Botta
- 关键词：Pyrazolo-pyrimidines ; Cyclodextrins ; Inclusion complexes ; Leukemia ; Anti-Proliferative ; Src/Abl dual inhibitors
- 刊名：European Journal of Medicinal Chemistry
- 出版年：2010
- 出版时间：December 2010
- 年：2010
- 卷：45
- 期：12
- 页码：5958-5964
- 全文大小：572 K
文摘
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.