Crystal structure, in vitro cytotoxicity, DNA binding and DFT calculations of new copper (II) complexes with coumarin-amide ligand

This work describes the synthesis, anticancer activity and electron structure study of two Cu (II) complexes with coumarin-3-formyl-(3-(aminomethyl) pyridine) ligand ( L ) - C1 (Cu 2 L 2 (OAc) 4 ) and C2 (CuL 2 (NO 3 ) 2 ). The structure of C1 and C2 was confirmed by elemental analysis , FTIR, and single-crystal X-ray analysis. Complex C1 crystallizes as binuclear where two Cu (II) ions are bridged by four acetate ligands while C2 is a mononuclear complex with twisted octahedral geometry. Density functional theory (DFT) calculations revealed that electronic transitions originate from metal-ligand charge transfer and d - d transitions of metal ions . According to the results of UV–Vis and fluorescence titrations, C1 and C2 intercalate with DNA with the binding constants of 6.9 × 10 5  M −1 and 5.9 × 10 5  M −1 , respectively. The in vitro cytotoxicity assays on four cancer cell lines (HeLa, HepG2, MCF-7 and A549) and a normal HUVEC cell line indicated higher anti-MCF-7 activity of C2 compared with cisplatin (IC 50  = 2.86 ± 0.08 μM vs. 9.07 ± 0.10 μM). Moreover, C2 had superior selectivity since IC 50 toward HUVEC cells was over 150 μM compared with 0.58 ± 0.05 μM for cisplatin. We concluded that the anti-MCF activity of mononuclear C2 complex is better than that of binuclear C1 and cisplatin. Therefore, C2 has been selected as a hit compound to develop novel non‑platinum anticancer agents through modification of coumarin-amide structure and variation of copper (II) salts.