Design, antibacterial activity, DNA interaction, anticancer and molecular docking analysis of novel bivalent metal chelates based on an no- donor schiff base ligand

Abstract Bivalent metal complexes of a Schiff base (HL) were synthesized via condensation of 2-amino-3-hydroxypyridine and 2,4-dihydroxybenzaldehyde. The prepared complexes were analyzed using FTIR, UV–visible, 1 H NMR, elemental analysis, magnetic moment, x-ray diffraction, molar conductance, and TGA. General formula [M(L) 2 (OH 2 ) 2 ] nH 2 O was suggested for complexes based on the elemental analysis results, at which M = Cu(II) (1); n = 2, Co(II) (2); n = 3/2, Ni(II) (3); n = 0.5, Mn(II) (4); n = nill and [UO 2 (L) 2 ] (5). Molar conductance measurements indicated that metal chelates are all non-electrolytes. Using donor sites of azomethine-N and phenolic-(2-OH), FTIR results demonstrated HL is bidentately coupled to metal ions. It is discovered that these complexes have octahedral geometrical structures based on the data from the electronic spectra and magnetic moment. These chelates’ thermal behavior demonstrated the eventual breakdown of the ligand molecules and water molecules. The intercalation of HL Schiff base ligand and complexes (1–5) with calf thymus DNA was measured and determined by electronic absorption spectroscopy. Antibacterial characteristics of ligand and complexes were investigated using catalase and peroxidase activity assays, MIC, MBC, and agar well diffusion. Biological properties of the Schiff base ligand (HL) and its metal complexes showed that metal complexes exhibited more antibacterial action than ligand. The inhibitory zones of complex (3) against the investigated bacteria ranged from 6 to 15 mm, with B. cereus being the exception. Ligand and complexes showed inhibition zones ranging 6–19 mm against all tested microorganisms. MIC values of ligand and complexes varied from 10 to 150 µg/ml. Complete inhibition of tested bacteria including drug-resistant P. aeruginosa bacterium, was achieved with 150 µg/ml from the prepared compounds that indicated the ability to apply them in different medical and industrial fields. This study investigates the molecular docking interactions of ligand and its metal complexes with key cancer targets: triple-negative breast cancer (TNBC, PDB ID 5HG8), hepatocellular carcinoma (HCC, PDB ID 3WZE), and leukemia (BCL-2, PDB ID 6O0K). Docking simulations evaluated binding affinities, interaction profiles, and binding energies. Interaction analysis revealed that metal coordination improved hydrogen bonding and π-interactions. These findings suggest metal complexation as a promising strategy for enhancing ligand efficacy in cancer therapy.