Design, synthesis, anticancer and molecular docking study of furo[2,3-c]quinolone derivatives

Abstract

Herein, we synthesized a series of furo[2,3-c]quinolone derivatives (3a–z′) using 2-(furan-3-yl)aniline derivative (1) and substituted benzylamine (2) in nitrobenzene using 1,10-phenanthroline-5,6-dione (phd)/FeCl₃ as a catalyst/p-toluene sulfonic acid (TsOH·H₂O) as an additive under aerial conditions at 80 °C, affording the products in moderate to good yields. All the synthesized compounds were screened for anticancer activity against KAMRC2, MDAMB231 and HCT8 cell lines. Cell death behaviour was investigated through high-content imaging (HCI), and compound 3h demonstrated a dose-dependent cytotoxic effect that was higher in KAIMRC2 than in HCT8. Further, TEM images of KAIMRC2 cells after treatment with compound 3h revealed cell shrinkage, nuclear condensation and nuclear membrane rupture. Complete wound closure was observed for KAIMRC2 and HCT8, indicating a high level of cell migration and proliferation in the wound healing assay. Western blot analysis was also performed to evaluate the expression levels of anti- and pro-apoptotic markers. Furthermore, to rationalize the observed biological activity, molecular docking was carried out to understand the binding affinity and binding interactions. This revealed a significant correlation between these compounds’ binding score and biological activity. The results of the in vitro and in silico studies suggest that the furo-quinoline derivatives represent ideal structural frameworks for therapeutic development.