Quinone-Fused Pyrazoles through 1,3-Dipolar Cycloadditions: Synthesis of Tricyclic Scaffolds and in vitro Cytotoxic Activity Evaluation on Glioblastoma Cancer Cells.
ChemMedChem
; 13(17): 1744-1750, 2018 09 06.
Article
em En
| MEDLINE
| ID: mdl-29966045
ABSTRACT
A novel and straightforward synthesis of highly substituted isoquinoline-5,8-dione fused tricyclic pyrazoles is reported. The key step of the synthetic sequence is a regioselective, Ag2 CO3 promoted, 1,3-dipolar cycloaddition of C-heteroaryl-N-aryl nitrilimines and substituted isoquinoline-5,8-diones. The broad functional group tolerability and mild reaction conditions were found to be suitable for the preparation of a small library of compounds. These scaffolds were designed to interact with multiple biological residues, and two of them, after brief synthetic elaborations, were analyzed by molecular docking studies as potential anticancer drugs. In vitro studies confirmed the potent anticancer effects, showing promising IC50 values as low as 2.5â
µm against three different glioblastoma cell lines. Their cytotoxic activity was finally positively correlated to their ability to inhibit PI3K/mTOR kinases, which are responsible for the regulation of diverse cellular processes in human cancer cells.
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Texto completo:
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pirazóis
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Benzoquinonas
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Neoplasias do Sistema Nervoso Central
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Glioblastoma
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Inibidores de Proteínas Quinases
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Antineoplásicos
Limite:
Humans
Idioma:
En
Revista:
ChemMedChem
Ano de publicação:
2018
Tipo de documento:
Article