Synthesis, spectral analysis, XRD, molecular docking simulation of dithranol and glycine mixed ligand complexes and their potential role in suppressing breast cancer cells via down‐regulating the expression of protein metalloproteinase‐9

Abstract

Five novel complexes of nickel (II)( 1 ), zinc (II)( 2 ), zirconium (IV)( 3 ), lanthanum (III)( 4 ), thorium (IV)( 5 ), with the dithranol ( Dithr ) ligand and glycine ( Gly ) were synthesized and characterized. Their structures were investigated using elemental analysis, molar conductance (Λ), magnetic studies ( μ eff ), spectroscopic methods (FT‐IR, UV–Vis., 1 H NMR, XRD), mass spectrometry, TG/DTG and DTA. Findings revealed that Dithr was chelated via two hydroxyl oxygen atoms and carbonyl group while, Gly chelated through carboxylic oxygen and nitrogen atom. All complexes appeared with molar ratio 1:1:1 ( M : Dithr : Gly ) and were electrolytes with 1:1 for ( 1 ), ( 2 ) and ( 3 ) complexes, 1:2 for ( 4 ) complex, and 1:3 for ( 5 ) complex according to elemental analysis and molar conductivity data. All metal‐chelates, except Th (IV)‐complex, were confirmed to have lattice water molecules based on their thermal behavior. Average crystalline size of all compounds was calculated using XRD analysis and found in the range 35.50–55.57 nm, indicating the compounds existed as nanocrystalline structure, except zirconium (IV) complex. Then, we studied cytotoxic effects of our synthetic drugs on the survival of an aggressive‐breast‐cancer‐histotype“66cl‐4.” Given its involvement in cancer‐metastasis, matrix‐metalloproteinase‐(MMP)‐9 protein expression was evaluated using western‐blotting‐assays. Th(IV)‐complex emerged as the most effective option in inhibiting cancer‐cells‐proliferation (IC 50 : 9.39 μM), and suppressed expression MMP‐9 levels by 86%, at 25 μM dose, and drug‐binding‐affinity was interpreted via molecular modeling.