Design, synthesis, TD-DFT, ADMET, molecular docking, and biological evaluation of novel 1,5-naphthyridine derivatives

A new series of 1,5‑naphthyridine derivatives (4a–4i) was synthesized, characterized using FT‑IR, NMR, and mass spectrometry, and subjected to Time-dependent density functional theory (TD-DFT) studies and biological assays. The study evaluated the binding affinities and interactions of naphthyridine derivatives as potential therapeutic agents. The Anticancer, antioxidant, and anti-inflammatory properties were correlated with the red shift in the UV spectra of the nitro-substituted molecules (4d–4f), and confirmed that a decrease in the HOMO-LUMO energy gap led to an increase in electrophilicity. The docking trial evaluated PDBs 5L2I, 9HWQ, and 6O0K with 1,5- naphthyridine analogs as anti-inflammatory, antioxidant, and anticancer targets based on pharmacological properties. Compound 4e (R = NO2, R1 = CH3) was identified as a potential lead compound, exhibiting increased cytotoxicity against MCF‑7 cells (IC50 = 5.2 ± 1.24 µM), A‑549 (IC50 = 6.2 ± 0.35 µM), and HeLa (IC50 = 5.4 ± 0.26 µM) cells, increased antioxidant activity (EC50 = 6.1 ± 0.42 µM), and anti-inflammatory activity (IC50 =7.2 ± 1.33 µM).