Novel Barbituric Acid–Derived Hydrazone Ni(II) Complexes: Synthesis, Structural Characterization, DNA Interactions, and Cytotoxic Evaluation
Sultan Kıncal, Cansu Topkaya, EsinSakallı Çetin, Ramazan GüpABSTRACT
Two new hydrazone‐oxime ligands and their dinuclear Ni(II) complexes, derived from 5‐acetylbarbituric acid with isonitrosophenylhydrazine and p‐chloroisonitrosophenylhydrazine, were synthesized and characterized by FTIR, UV‐Vis, NMR, MALDI‐TOF‐MS, elemental, and magnetic analyses, confirming their square‐planar geometry. DNA‐binding studies indicated mainly electrostatic interactions, while gel electrophoresis revealed both oxidative and hydrolytic cleavage involving reactive oxygen species. Topoisomerase IIα inhibition assays showed catalytic inhibition at 5 µM. Cytotoxicity (MTT) tests against CACO‐2, LnCap, and MDA‐MB‐231 cells demonstrated time‐ and dose‐dependent antiproliferative effects. [Ni 2 (L 1 ) 2 ] was most active on LnCap (IC 50 = 27.4 µM) and [Ni 2 (L 2 ) 2 ] showed strong selectivity toward MDA‐MB‐231 (IC 50 = 5.93 µM). Though less potent than cisplatin, both were comparable to etoposide with better selectivity, suggesting barbituric acid–based Ni(II) complexes as promising anticancer candidates.