Synthesis, structural characterization, biological and in silico evaluation of halogenated Schiff bases as potential multifunctional agents

• Three new halogen substituted Schiff bases (SB1, SB2, and SB3) were synthesized. • Detailed spectroscopic and theoretical investigations were carried out. • All compounds were tested for cyto-toxicity, antioxidant, and antibacterial. • Biological study results revealed SB1 and SB3 as the most potent across all the assays, with SB1 been more superior. The rising global burden of antimicrobial resistance, oxidative stress–related disorders, and cancer has intensified the search for multifunctional molecules with broad therapeutic potential. In this study, three halogen-substituted Schiff bases (SB1–SB3) were synthesized via the condensation of 2‑tert-butylaniline with 3,5-dichloro-, 3,5-dibromo-, and 3,5-diiodosalicylaldehyde, respectively. The compounds were characterized using FTIR, UV–Vis, 1 H and 13 C NMR, mass spectrometry, CHN elemental analysis, and single-crystal X-ray diffraction to confirm their structural integrity and purity. Cytotoxicity screening against the ME180 cervical cancer cell line revealed potent activity, with SB2 (bromo‑substituted) showing the lowest IC₅₀ (0.60 μM), followed by SB1 (chloro, 0.72 μM) and SB3 (iodo, 1.03 μM). Antioxidant evaluation using the DPPH radical scavenging assay indicated moderate, dose-dependent activity, with SB1 exhibiting the highest scavenging rate (37.6–38.8 %). Antibacterial assays against Staphylococcus. aureus, Staphylococcus. pyogenes, Escherichia coli , and Klebsiella. pneumoniae demonstrated SB1’s superior inhibitory effect and lowest MIC values, particularly against S. pyogenes and K. pneumoniae .Computational analyses, including molecular docking, molecular dynamics simulations (MDS), and ADMET profiling, supported the experimental findings. The compounds exhibited favourable binding affinities, especially through Zn²⁺ coordination and interactions with Glu402 and His411. MDS confirmed the stability of SB1 and SB3 over 150 ns, while ADMET results highlighted SB1’s promising drug-like characteristics.