Synthesis and antiproliferative activity of 6,7-disubstituted-4-phenoxyquinoline derivatives bearing the 1,8-naphthyridin-2-one moiety.
Eur J Med Chem
; 158: 201-213, 2018 Oct 05.
Article
in En
| MEDLINE
| ID: mdl-30216852
ABSTRACT
A series of 6,7-disubstituted-4-phenoxyquinoline derivatives bearing the 1,8-naphthyridin-2-one moiety were designed, synthesized and evaluated for their biological activities. The target compounds exhibited moderate to high antiproliferative activity against three cancer cell lines (A549, HepG2 and MCF-7) and several compounds (25, 27, 33, 37, 41, 43, 49 and 53) were evaluated for the activity against c-Met kinase. The most promising compound 33 (IC50 c-Metâ¯=â¯2.36â¯nM) showed excellent activity against A549, HepG2 and MCF-7â¯cell lines with IC50 values of 0.23⯵M, 0.42⯵M and 0.21⯵M, respectively, which was 1.5-2.1 times of the positive control. Furthermore, compound 33 was evaluated for the activity against Flt3, PDGFR-α, PDGFR-ß, c-Kit, Flt4, ALK and EGFR kinase. Structure activity relationship studies indicated that mono-EWGs (such as R2â¯=â¯F) at 4-position of moiety C was a key factor in improving the antitumor activity. In addition, further research on compound 33 was mainly including concentration dependence, apoptosis (acridine orange staining), apoptosis result analyzing and molecular docking.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Quinolines
/
Cell Proliferation
/
Naphthyridines
/
Antineoplastic Agents
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Eur J Med Chem
Year:
2018
Type:
Article