Zinc complex with quinoline-based thiazolyl-hydrazone targeting DNA replication in cancer cells

Area of Science:

• Medicinal Chemistry
• Inorganic Chemistry
• Cancer Biology

Background:

• Developing selective anticancer agents is a key goal in medicinal chemistry.
• Metal complexes offer potential for enhanced therapeutic efficacy.
• Hybrid ligands combining heterocyclic scaffolds and metal ions are promising.

Purpose of the Study:

• To synthesize and characterize a novel zinc(II) complex with a quinoline-based thiazolyl-hydrazone ligand.
• To evaluate the in vitro and in vivo anticancer activity and selectivity of the complex.
• To elucidate the mechanism of action of the zinc complex in cancer cells.

Main Methods:

• Synthesis and structural characterization of the zinc(II) complex.
• In vitro cytotoxicity assays against cancer and non-cancer cell lines.
• Mechanistic studies including cell cycle analysis, DNA synthesis inhibition, apoptosis assays, and mitochondrial function assessment.
• In vivo studies using 3D spheroids and the chick chorioallantoic membrane model.

Main Results:

• The synthesized zinc(II) complex exhibits potent and selective cytotoxicity against A-549 lung and HCT-116 colorectal cancer cells, sparing HEK-293 cells.
• The complex induces S-phase arrest, inhibits DNA synthesis, and triggers apoptosis via the intrinsic pathway, evidenced by DNA damage and caspase activation.
• In vivo studies demonstrate tumor growth inhibition in 3D spheroids and the chick chorioallantoic membrane model with no significant toxicity.

Conclusions:

• The zinc(II) complex demonstrates superior efficacy and selectivity compared to the free ligand and existing chemotherapeutics.
• Metal coordination enhances the biological activity of the hybrid ligand, suggesting a promising strategy for developing novel anticancer agents.
• This study supports the further development of this class of metal complexes as targeted anticancer therapeutics.