Design and synthesis of 7-alkoxy-4-heteroarylamino-3-quinolinecarbonitriles as dual inhibitors of c-Src kinase and nitric oxide synthase.
Because both c-Src and iNOS are key regulatory enzymes in tumorigenesis, a new series of 4-heteroarylamino-3-quinolinecarbonitriles as potent dual inhibitors of both enzymes were designed, prepared, and evaluated for blocking multiple signaling pathways 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 could inhibit both enzymes, and several of them showed potent inhibition activity against different cancer cell lines. The best compound 20 (CPU-Y020) showed the IC(50) values of 6.58 and 7.61microM toward colon cancer HT-29 and liver cancer HepG2 cell lines.
Cao
Xin
X
Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing 210009, China.
You
Qi-Dong
QD
Li
Zhi-Yu
ZY
Guo
Qing-Long
QL
Shang
Jing
J
Yan
Ming
M
Chern
Ji-Wang
JW
Chen
Men-Ling
ML
D000081247:CSK Tyrosine-Protein Kinase; D045744:Cell Line, Tumor; D015195:Drug Design; D006131:Growth Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D019073:HT29 Cells; D006801:Humans; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors*; D009570:Nitriles / Q000138:chemical synthesis* / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011804:Quinolines / Q000138:chemical synthesis* / Q000494:pharmacology; D019061:src-Family Kinases
D006131:Growth Inhibitors; D009570:Nitriles; D047428:Protein Kinase Inhibitors; D011804:Quinolines; D052247:Nitric Oxide Synthase Type II; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; C000631346:CSK protein, human