The design, synthesis and anticancer activity of 4-heteroarylamino-3-cyanoquinolines as dual inhibitors of c-Src and iNOS

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 0.048 4 μmol×L^-1 and 34.5 μmol×L^-1, respectively.  Some of the compounds also showed moderate anti-proliferation activities at 10 μmol×L^-1 against colon cancer HT-29 and liver cancer HepG2 cell lines.