A multifaceted approach to novel (E)-3-(4-bromobenzylidene)-1,8-naphthyridine-2,4(1H,3H)-dione: synthesis, biological screening, DFT and molecular docking studies

A novel (E)-3-(4-bromobenzylidene)-1,8-naphthyridine-2,4(1H,3H)-dione derivative was synthesized and evaluated for its anticancer potential. The chemical formula and structure of the synthesized derivative was obtained using different spectroscopic techniques. Molecular structure optimization of the synthesized compound was performed using B3LYP/6–311++G (d,p) level of theory. The UV–Vis spectrum showed strong charge transfer transitions (π–π*) with high extinction coefficient (0.9869). The NBO analysis showed orbital overlap between π (C2-N11) and π*(C3-C4) due to the intramolecular charge transfer. The first hyperpolarizability (β0) was found to be 47.074 × 10−30esu, showed that the molecule can be a better option for NLO applications as compared to the standard reference urea. The global reactivity descriptors were also correlated with the biological properties of the compound. The moderate activity against HeLa cell line of the synthesized compound was reflected from its IC50 value (230 μM), QTAIM framework and Reduced Density Gradient were used to describe the nature of various intermolecular interactions and showed two closed-shell interactions (O13 – H18 and O15 – H23) with calculated bond energies of −5.0828 kJ/mol and −6.1495 kJ/mol, respectively. The reactivity sites were identified by mapping the electron density into Molecular Electrostatic Potential (MEP) and indicated that in the molecule the most electrophilic sites are the nitrogen of NH and phenyl ring. Docking studies were performed to examine binding sites of the titled molecule and the total binding energy and inhibition constant of compound were found to be −7.89 Kcal/mol and 1.65 µM exhibiting good binding affinity with the protein HER2 kinase. The bioactivity scores indicated drug-likeness of the synthesized molecule. Naphthyridine-2,4-dione derivative (3) was synthesized.The synthesized molecule was evaluated by various spectroscopic techniques.DFT studies of the compound 3 were done.The compound 3 exhibited moderate activity against HeLa cell line.Potential of the synthesized molecule was assessed by molecular docking & ADMET. Naphthyridine-2,4-dione derivative (3) was synthesized. The synthesized molecule was evaluated by various spectroscopic techniques. DFT studies of the compound 3 were done. The compound 3 exhibited moderate activity against HeLa cell line. Potential of the synthesized molecule was assessed by molecular docking & ADMET.