Synthesis and anticancer activity of cyclometalated Pt(<scp>ii</scp>) neutral complexes containing curcumin as a bioactive ancillary ligand

A novel series of cyclometalated platinum(II) complexes of curcumin, [(C^N)Pt(curc)] 1-5, was synthesized <i>via</i> a microwave-assisted procedure, using NEt₃ as the base, which offers a safer and more efficient alternative to traditional synthetic methods. The complexes were obtained in high yields and fully characterized through spectroscopic and analytical techniques. Structural and spectroscopic data confirmed the coordination of curcumin to the Pt(II) center, with notable shifts in IR and NMR signals supporting metal-ligand interactions. Lipophilicity studies revealed log <i>P</i> values ranging from 3.15 to 3.76, consistent with favorable membrane permeability and drug-likeness. Photophysical characterization showed that all complexes exhibited broad absorption bands with LMCT and π-π* transitions and dual fluorescence emission bands, indicating the presence of coordinated species. Over time, a slow release of curcumin in solution was detected, although complexes remained stable under physiological conditions for at least 72 h, as confirmed by absorption studies. The antiproliferative activity of complexes 1-5 was initially screened on human fibroblasts, leading to the selection of complexes 3, 4 and 5 for further evaluation on cancer cell lines. Complexes 4 and 5 showed notable cytotoxicity, particularly against SK-ES1 (Ewing's sarcoma), with IC₅₀ values of 15.4 μM and 13.9 μM, respectively. These compounds maintained significant activity over 72 h, aligning with their spectroscopic stability. Given their potency, selectivity and lack of photoactivation requirement, complexes 4 and 5 emerged as promising candidates for the treatment of Ewing's sarcoma.