Synthesis, characterization, DFT analysis, and molecular docking studies of carbothioamide Schiff base-phenanthroline...

This study reports the synthesis and biomedical evaluation of novel ternary metal complexes based on a tridentate Schiff base ligand (CHPT) and 1,10-phenanthroline (PHEN) as a co-ligand. The ligand, (Z)-2-((E)-1-(2-(4-chlorophenyl)hydrazineylidene)propan-2-ylidene)-N-phenylhydrazine-1-carbothioamide, was used to construct Fe(III), Co(II), and Cu(II) complexes. The complexes were characterized using elemental analysis, FT-IR, UV-Vis, mass spectroscopy, and conductivity measurements. All complexes exhibited distorted octahedral geometries. Density Functional Theory (DFT) calculations (B3LYP/LANL2DZ) provided insight into electronic properties, including HOMO-LUMO gaps, chemical reactivity, and electrostatic potential. Biological screening revealed significant antimicrobial activity, with the Cu(II) complex displaying the highest potency against Gram-positive and Gram-negative bacteria, as well as Candida albicans. The Cu(II) complex also exhibited strong anti-H. pylori activity and superior anticancer efficacy against MCF-7 breast cancer cells (IC₅₀ = 10.5 µg/mL), while maintaining low toxicity toward normal VERO cells. It also showed promising activity against K-562 leukemia cells (IC₅₀ = 287.19 µg/mL). Molecular docking studies supported the multi-target potential of the Cu(II) complex by confirming stable binding with key therapeutic targets such as FLT3 kinase, BCL-2, IDH2 R140. Furthermore, Swiss ADME predictions confirmed that the Cu(II) complex possesses favorable drug-likeness, bioavailability, and low CYP-mediated interaction risks, supporting its potential as a multi-target therapeutic agent.