Design, Synthesis, Characterization and Evaluation of Anticancer Activity of Substituted-4-(Substitutedphenylhydrazono)-3,4-Dihydroquinolin-2-(1H)-One

Abstract

Background: Hepatocellular carcinoma (HCC) remains a therapeutically challenging malignancy due to limited treatment options and toxicity associated with current chemotherapeutic and targeted agents. The current investigation deals with the design, synthesis, characterization, in silico studies of a series of 4- (2-substitutedphenylhydrazono)- 6-substituted-3,4-dihydroquinolin-2(1H)-one derivatives and screening for their in vitro anticancer activity against HCC by sulforhodamine B assay. Materials and Methods: All the synthesised compounds were characterised by ultraviolet-visible, Fourier transform infrared, nuclear magnetic resonance (1 H and13C) and mass spectroscopy. Results and Discussion: Docking studies of all the synthesized compounds revealed favorable docking score utilising the epidermal growth factor receptor (EGFR)-tyrosine kinase binding site (Protein Data Bank: 1m17), with compound 4-(2-(2,4-dinitrophenyl)hydrazono)-6-fluoro-3,4 dihydroquinolin-2(1H)-one (IIIc_4) showing the highest molecular docking (MolDock) score of −104.42, which is comparable to reference drug Imatinib with a MolDock score of −109.39 and found to be more effective than standard drug Adriamycin which showed MolDock score of −76.67. Among the screened derivatives, three of the derivatives, that is, compound 4-(2-(2,4-dinitrophenyl)hydrazono)-3,4-dihydroquinolin-2(1H)- one (IIIa_4); 6-chloro-4- (2-(2,4-dinitrophenyl) hydrazono)-3,4 dihydroquinolin-2 (1H)-one (IIIb_4) and 4-(2-(2,4 dinitrophenyl)hydrazono)-6-fluoro-3,4- dihydroquinolin-2(1H)-one (IIIc_4), had an inhibitory effect on cell growth with GI50 <10 μg/mL when compared to positive control Adriamycin. Conclusion: The combined computational and biological data suggest that these hydrazinoquinoline derivatives, especially those with electron-withdrawing substituents, hold promise as lead structures for further development in liver cancer therapy targeting EGFR. Future studies would focus on their detailed mechanism, selectivity, and in vivo efficacy to validate their therapeutic utility