Synthesis, Characterization and in vitro Anticancer Evaluation of Novel Quinoline-3- Carboxamide Derivatives as Inhibitors of PDGFR

Cancer cells exploit transmembrane receptor protein kinases like platelet derived growth factor (PDGF) for their survival, which leads to the development of resistance towards anticancer agents. The importance of inhibiting PDGF receptor is well established. In this article, twelve novel substituted 2-aminoquinoline-3-carboxamide derivatives were synthesized from substituted anilines using Vilsmeier–Haack reaction, producing 2-chloro-3-carbaldehyde quinolines, followed by oxidation of 2-chloro-3-carbaldehyde to the carboxylic acid and coupling this group with various anilines done by using dicyclohexylcarbodiimide (DCC) coupling reagent to form amide bonds as potential inhibitors of PDGFR is reported. The structures of the synthesized compounds were confirmed by IR, 1H NMR, 13C NMR and mass spectrometry. SAR studies suggested the importance of the electron-donating nature of the R group for the molecule to be toxic. The cytotoxicity assay of synthesized compounds was performed against breast cancer cell line (MCF-7) and found promising results. The results obtained in vitro cytotoxicity evaluation study revealed the superior activity of three derivatives (6a, 6b, and 6i) compared with that of imatinib. In conclusion, these experiments will lay the groundwork for the evolution of potent and selective PDGFR inhibitors for the treatment of cancer cells.