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.
Dreassi, E., Zizzari, A.T., Mori, M., Filippi, I., Belfiore, A., Naldini, A., et al. (2010). 2-Hydroxypropyl-β-cyclodextrin strongly improves water solubility and anti-proliferative activity of pyrazolo[3,4-d]pyrimidines Src-Abl dual inhibitors. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 45(12), 5958-5964 [10.1016/j.ejmech.2010.09.062].
2-Hydroxypropyl-β-cyclodextrin strongly improves water solubility and anti-proliferative activity of pyrazolo[3,4-d]pyrimidines Src-Abl dual inhibitors
Dreassi, Elena;Zizzari, ALESSANDRA TANIA;Mori, Mattia;Filippi, Irene;Belfiore, Amalia;Naldini, Antonella;Carraro, Fabio;Santucci, Annalisa;Botta, Maurizio
2010-01-01
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.
| File | Dimensione | Formato | |
|---|---|---|---|
|
ciclodestrine 2010.pdf
non disponibili
Tipologia:
Post-print
Licenza:
NON PUBBLICO - Accesso privato/ristretto
Dimensione
572.26 kB
Formato
Adobe PDF
|
572.26 kB | Adobe PDF | Visualizza/Apri Richiedi una copia |
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
https://hdl.handle.net/11365/21004
Attenzione
Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo