Metallo-hydrazones of pyridine–thiophene derivatives: structure–function insight and anticancer evaluation of Co(iii), Ni(ii), Cu(ii), and Zn(ii) complexes

Abstract

Metal-based chemotherapeutic agents have attracted considerable attention for their ability to disrupt essential cellular processes. A series of complexes [Co(ptch)₂]0.5CoCl₄·H₂O (1), [Ni(ptch)₂] (2), [Cu(ptch)₂]CHCl₃ (3), and [Zn(ptch)₂] (4) were synthesized by 2-pyridinecarbaldehyde-thiophene-2-carboyl hydrazone (Hptch). The ligand and its metal complexes 1–4 were characterized through elemental analysis and various spectroscopic techniques, viz. FT-IR, UV-vis, NMR, and single-crystal X-ray diffraction data, confirming their proposed structures and coordination modes. SC-XRD confirmed distorted octahedral geometries around metal centres. Molecular docking studies were performed against human Carbonic Anhydrase II (PDB ID: 6vj3) to evaluate the binding affinity of the ligand and its metal complexes. Among the tested compounds, complex 4 exhibited the most favorable binding interactions, suggesting a strong and stable interaction with the active site of the target protein, corroborating its enhanced biological potential. Furthermore, the in vitro anticancer activity of the synthesized complexes was assessed against the MDA-MB-231 human breast cancer cell line using the standard MTT assay, revealing notable cytotoxic effects indicative of their potential as effective anticancer agents. Complexes 1 (IC₅₀ = 4.19 ± 0.03 µg mL⁻¹) and 4 (IC₅₀ = 4.00 ± 0.68 µg mL⁻¹) exhibit significant cytotoxicity against breast cancer (MDA-MB-231) cells, with complex 4 displaying superior efficacy based on both IC₅₀ value and molecular docking scores. These findings suggest that complexes 1 and 4, in particular, possess strong anticancer potential, likely mediated via apoptotic pathways.