New pyridopyrimidine derivatives as dual EGFR and CDK4/cyclin D1 inhibitors: synthesis, biological screening and molecular modeling.
Future Med Chem
; 16(16): 1633-1648, 2024 Aug 17.
Article
de En
| MEDLINE
| ID: mdl-39023284
ABSTRACT
Aim:
A series of pyridopyrimidine derivatives 5-20 was designed, synthesized and examined for antitumor activity using four types of malignant cells.Materials &methods:
Cervical cancer (HeLa), hepatic cancer (HepG-2), breast cancer (MCF-7) and colon cancer (HCT-166) cells, as well as normal human lung fibroblast cells (WI-38) were used to determine the cytotoxicity.Results:
Pyrazol-1-yl pyridopyrimidine derivative 5 was found to be the most active compound against three malignant cells Hela, MCF-7 and HepG-2 with IC50 values of 9.27, 7.69 and 5.91 µM, respectively, related to standard Doxorubicin. Moreover, compounds 5 and 10 showed good inhibition against cyclin dependent kinase (CDK4/cyclin D1) and epidermal growth factor (EGFR) enzymes.
[Box see text].
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Pyrimidines
/
Tests de criblage d'agents antitumoraux
/
Cycline D1
/
Inhibiteurs de protéines kinases
/
Kinase-4 cycline-dépendante
/
Récepteurs ErbB
/
Antinéoplasiques
Limites:
Humans
Langue:
En
Journal:
Future Med Chem
Année:
2024
Type de document:
Article
Pays d'affiliation:
Égypte
Pays de publication:
Royaume-Uni