title: Design and synthesis of 7-alkoxy-4-heteroarylamino-3-quinolinecarbonitriles as dual inhibitors of c-Src kinase and nitric oxide synthase.
abstract: 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.
authors.affiliation: Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Cao
authors.forename: Qi-Dong
authors.initials: QD
authors.lastname: You
authors.forename: Zhi-Yu
authors.initials: ZY
authors.lastname: Li
authors.forename: Qing-Long
authors.initials: QL
authors.lastname: Guo
authors.forename: Jing
authors.initials: J
authors.lastname: Shang
authors.forename: Ming
authors.initials: M
authors.lastname: Yan
authors.forename: Ji-Wang
authors.initials: JW
authors.lastname: Chern
authors.forename: Men-Ling
authors.initials: ML
authors.lastname: Chen
mesh_terms: 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
chemical_list: 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