Identification of new potent phthalazine derivatives with VEGFR-2 and EGFR kinase inhibitory activity.
Eur J Med Chem
; 123: 191-201, 2016 Nov 10.
Article
in En
| MEDLINE
| ID: mdl-27484508
ABSTRACT
Efforts to develop new antitumor agents are now directed towards multitarget therapies that are believed to have high potency and low tendency to resistance compared to conventional drugs. Herein, we highlighted the synthesis and antitumor activity of five series of phthalazine-based compounds featuring a variety of bioactive chemical fragments at position 1 of the phthalazine nucleus. The antitumor activity of the target compounds was performed against fourteen cancer cell lines where all compounds were active in the nanomolar level. In addition, the mechanism of action of the target compounds was investigated through an enzymatic inhibitory assay against VEGFR-2 and EGFR kinases, revealing potent and preferential activity toward VEGFR-2. Binding mode of the most active compounds was studied using docking experiment.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Phthalazines
/
Vascular Endothelial Growth Factor Receptor-2
/
Protein Kinase Inhibitors
/
ErbB Receptors
/
Antineoplastic Agents
Type of study:
Diagnostic_studies
/
Prognostic_studies
Limits:
Humans
Language:
En
Year:
2016
Type:
Article