1. Pyrazole[3,4-d]pyrimidine derivatives loaded into halloysite as potential CDK inhibitors
- Author
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Aldo Di Leonardo, Patrizia Cancemi, Silvia Schenone, Marina Massaro, Fabrizio Lo Celso, César Viseras Iborra, Serena Riela, Giancarlo Grossi, Viviana Barra, Giampaolo Barone, Università degli Studi di Palermo, Massaro M., Barone G., Barra V., Cancemi P., Di Leonardo A., Grossi G., Lo Celso F., Schenone S., Viseras Iborra C., and Riela S.
- Subjects
Cell cycle checkpoint ,Pyrimidine ,Pharmaceutical Science ,02 engineering and technology ,CDK inhibitors ,Halloysite ,Nanocomposites ,Pyrazolo[3,4-d]pyrimidine derivatives ,Cell Cycle Checkpoints ,Cell Line, Tumor ,Clay ,Humans ,Pyrazoles ,Pyrimidines ,Pyrazole ,030226 pharmacology & pharmacy ,Cell Line ,HeLa ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Cyclin-dependent kinase ,Pyrazolo[3 ,Settore BIO/06 - Anatomia Comparata E Citologia ,Settore CHIM/02 - Chimica Fisica ,Tumor ,biology ,Chemistry ,Kinase ,Cell growth ,4-d]pyrimidine derivatives ,Settore CHIM/06 - Chimica Organica ,Cell cycle ,021001 nanoscience & nanotechnology ,biology.organism_classification ,Settore BIO/18 - Genetica ,Settore CHIM/03 - Chimica Generale E Inorganica ,biology.protein ,Cancer research ,0210 nano-technology - Abstract
Uncontrolled cell proliferation is a hallmark of cancer as a result of rapid and deregulated progression through the cell cycle. The inhibition of cyclin-dependent kinases (CDKs) activities is a promising therapeutic strategy to block cell cycle of tumor cells. In this work we reported a new example of nanocomposites based on halloysite nanotubes (HNTs)/pyrazolo[3,4-d]pyrimidine derivatives (Si306 and Si113) as anticancer agents and CDK inhibitors. HNTs/Si306 and HNTs/Si113 nanocomposites were synthesized and characterized. The release kinetics were also investigated. Antitumoral activity was evaluated on three cancer cell lines (HeLa, MDA-MB-231 and HCT116) and the effects on cell cycle arrest in HCT116 cells were evaluated. Finally, molecular dynamics simulations were performed of the complexes between Si113 or Si306 and the active site of both CDK 1 and 2., The work was financially supported by the University of Palermo. The work was carried out in the frame of the PON “AIM: Attrazione e Mobilità Internazionale” No. 1808223 project. SS and GG wish to acknowledge the AIRC project 2019 code 23725. The authors would thank Dr. Susanna Guernelli (University of Bologna) for TEM and SEM measurements.
- Published
- 2021