The design, synthesis and anticancer activity of 4-heteroarylamino-3-cyanoquinolines as dual inhibitors of c-Src and iNOS.
- Author:
Xin CAO
1
;
Qi-dong YOU
;
Zhi-yu LI
;
Qing-long GUO
;
Yong YANG
;
Jing SHANG
;
Ming YAN
;
Ji-wang CHEN
;
Meng-ling CHEN
Author Information
1. Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing 210009, China.
- Publication Type:Journal Article
- MeSH:
Aniline Compounds;
chemical synthesis;
chemistry;
pharmacology;
Antineoplastic Agents;
chemical synthesis;
chemistry;
pharmacology;
Cell Line, Tumor;
Cell Proliferation;
drug effects;
Drug Delivery Systems;
Drug Design;
Humans;
Nitric Oxide Synthase Type II;
antagonists & inhibitors;
metabolism;
Protein-Tyrosine Kinases;
antagonists & inhibitors;
metabolism;
Quinolines;
chemical synthesis;
chemistry;
pharmacology;
src-Family Kinases
- From:
Acta Pharmaceutica Sinica
2009;44(3):288-295
- CountryChina
- Language:Chinese
-
Abstract:
Because c-Src and iNOS are key regulatory enzymes in tumorigenesis, a new series of 4-heterocycle amine-3-quinolinecarbonitriles as potent dual inhibitors of both enzymes were designed, synthesized and evaluated as multiple targets agents in cancer therapy. All compounds were evaluated by two related enzyme inhibition assays and an anti-proliferation assay in vitro. The results showed that most compounds inhibited c-Src and iNOS well. The best compound 33 inhibited both enzymes with the IC50 values of 0.0484 micromol x L(-1) and 34.5 micromol x (-1), respectively. Some of the compounds also showed moderate anti-proliferation activities at 10 micromol x L(-1) against colon cancer HT-29 and liver cancer HepG2 cell lines.
