article · Applied Organometallic Chemistry
Five novel metal complexes incorporating dithranol and glycine were synthesised using nickel, zinc, zirconium, lanthanum, and thorium. Comprehensive characterisation confirmed a 1:1:1 metal-to-ligand ratio, with dithranol coordinating through two hydroxyl oxygen atoms and a carbonyl group, and glycine binding via a carboxylic oxygen and nitrogen. Except for the zirconium complex, the compounds exhibited nanocrystalline structures with crystallite sizes between 35.50 and 55.57 nanometres. Cytotoxic evaluations on the aggressive 66cl-4 breast cancer cell line revealed marked antiproliferative effects. The thorium(IV) complex demonstrated the strongest activity, achieving an IC50 of 9.39 micromolar. It also suppressed the expression of matrix metalloproteinase-9, a key protein involved in tumour metastasis, by 86 percent at a concentration of 25 micromolar, with molecular docking simulations supporting its binding behaviour.
Aggressive breast cancers often metastasise, making effective treatment difficult and highlighting the need for novel therapeutic agents. Matrix metalloproteinase-9 is an enzyme that facilitates cancer spread. Demonstrating that metal-based drug candidates can directly suppress this enzyme while killing aggressive cancer cells offers promising biochemical leads for tackling hard-to-treat malignancies.
This research is at an early experimental stage within medicinal chemistry. The findings could interest oncology drug discovery teams and pharmaceutical developers seeking new coordination complexes as therapeutic leads against metastatic breast cancer. Significant development hurdles remain, including extensive in vitro selectivity screens, in vivo safety and efficacy validation, and pharmacokinetic studies, placing any commercial application several years away.
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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.
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DOI: 10.1002/aoc.7650
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