Synthesis, molecular docking, antibacterial and anticancer activity of benzodioxine-coupled schiff base and metal complexes

Schiff base ligand (H2L) and its metal complexes (Co(II) and Cu(II)) have been synthesized from the reaction between 2,3-dihydrobenzo[b][1,4]Dioxine-6,7-diamine and 4-(diethylamino)-2-hydroxybenzaldehyde. The ligand and its complexes were characterized using FTIR, UV–Vis, elemental (CHN) analysis and mass spectrometry methods. The antibacterial activity of the Schiff base ligand (H2L) and its complexes was evaluated against S. aureus and Escherichia coli strains. The complexes with Cu(II) and Co(II) showed MIC values of 23.7 ± 0.2 μg/ml and 22.9 ± 0.1 μg/ml, respectively, at a concentration of 100 μg/ml, which were more favorable than the parent ligand. The antiproliferative activity of H2L and its Co(II) and Cu(II) metal complexes, have been evaluated using the MTT assay against human breast, lung, colorectal, and liver cancer cell lines. The Cu(II) complex showed the better anticancer activity against A549 (IC₅₀= 16.12±5.48 µg/mL), MCF-7 (IC₅₀= 13.18±4.14 µg/mL), HepG2 (IC₅₀= 15.18±5.48 µg/mL), and HCT116 (IC₅₀= 17.11±3.18 µg/mL) cell lines, with IC₅₀ values significantly lower than those of the Co(II) complex and the parent ligand. Additionally, computational studies at the B3LYP/6–311G++(d,p) and LANL2DZ basis sets provided insights into the electronic properties of the compounds, supporting the experimental results. Schiff base ligand and its metal complexes have also been docked against VEGFR2, ERK2, DNA gyrase, and SarA proteins. Molecular docking studies of the Cu(II) complex revealed strong binding affinities with target proteins VEGFR2, ERK2, DNA gyrase and SarA proteins with binding energies of -6.55, -8.85, -8.38 and -6.80 kcal/mol, respectively.