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 (Cu2L2(OAc)4) and C2 (CuL2(NO3)(2)). The struc-ture 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 x 105 M(-1 )and 5.9 x 105 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 (IC50 = 2.86 +/- 0.08 mu M vs. 9.07 +/- 0.10 mu M). Moreover, C2 had superior selectivity since IC50 toward HUVEC cells was over 150 mu M compared with 0.58 +/- 0.05 mu M 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.