Design, Synthesis, Characterization, and Antiproliferative Screening of New Metal Complexes from Heterocyclic Ligand System

Transition metal complexes with heteroaromatic ligands offer a promising strategy for developing novel anticancer agents. In this study, the ligand 12-hydroxy-7-iminocromeno[4,3- d]pyrido[1,2-a]pyrimidin-6(7H)-one was used to synthesize new cobalt(II), nickel(II), and titanium( III/IV) complexes via conventional and microwave-assisted methods, with the latter providing higher yields and shorter reaction times. The complexes were characterized by FT-IR, ¹H- and ¹³CNMR, mass spectrometry, and elemental analysis, confirming coordination through the azomethine nitrogen and phenolic oxygen atoms. Their in vitro antiproliferative activity was evaluated against the H460, MCF-7, and HCT116 human cancer cell lines, with doxorubicin used as a positive control. Cytotoxicity was expressed as GI₅₀ values. All complexes exhibited moderate to pronounced antiproliferative effects. The nickel(II) and cobalt(II) complexes showed moderate activity, whereas the titanium( III/IV) complexes were the most potent, displaying significantly higher cytotoxicity than the free ligand, with GI₅₀ values in the low micromolar range. These findings highlight the influence of the metal center on biological activity and identify the titanium complexes as promising candidates for further anticancer studies.