Evaluation of Schiff Bases Against Two Cancer Cell Lines: A Combined Experimental and Theoretical Approach

The rising global cancer rate necessitates the development of new therapeutic agents, with Schiff bases, compounds containing primary amines and aldehydes, gaining attention for their anticancer properties. The present study investigated the anticancer potential of three Schiff base derivatives against two cancer cell lines, MDA-MB231 (breast cancer) and HepG2 (liver cancer), employing both experimental and theoretical approaches. Schiff bases were synthesized using condensation reactions and characterized employing 1H-NMR, 13C-NMR, and mass spectrometry. Cytotoxicity was evaluated using the MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, and determined IC50 values. Computational studies using density functional theory (DFT) were employed to optimize molecular structures and assess electronic properties of Schiff bases, computing HOMO-LUMO energy gaps, dipole moments, and heat of formation. The three Schiff bases synthesized included (E)-4-(((4-chloro-2-nitrophenyl)imino)methyl)-3-methoxyphenol (1), 2-((2,4-dichlorophenylimino)methyl)-5-(diethylamino)phenol (2),  and (E)-4-(((4-chloro-2-nitrophenyl)imino)methyl)-3-methoxy-N,N-dimethylaniline (3). Compound 2 demonstrated the highest activity against the HepG2 cell line with an IC50 value of 43.17 µg/mL, while compounds 1 and 3 exhibited lower activities (IC50 values of 70.29 and 73.69 µg/mL, respectively). The compounds also showed varying degrees of activity against the MDA-MB231 cell line, with compound 2 being the most effective. Molecular docking simulations further supported the experimental results, highlighting significant binding interactions between compound 2 and breast cancer-related proteins, with the strongest binding observed to Akt (5KCV). Similarly, compound 1 demonstrated effective binding to liver cancer proteins. This combined experimental and theoretical study provides valuable insights into the anticancer activity of Schiff bases and highlights their potential as promising candidates for cancer therapy.