Molecular docking study and <i>in vitro</i> evaluation of apoptotic effect of biogenic-amine-based <i>N, O</i>-Cu(II) complexes as potent antitumor agents

In our attempts toward identifying biologically relevant metal compounds, two copper (II) complexes, <b>Cu1</b> and <b>Cu2,</b> have been prepared from the imines bearing tryptamine <b>1a</b>/or tyramine <b>1b</b> moieties in the structure as ligands. The X-ray crystal structure of the complex <b>Cu1</b> has been described for the first time and revealed a centrosymmetric complex possessing a CuN2O2 chromophore with square planar coordination geometry. <i>In vitro</i> evaluation of cytotoxic activity against several human cancer cells (U251, HCT116, and HeLa) and healthy MRC5 fibroblast cell line as control, has indicated a strong cytotoxic effect on the glioblastoma tumor cell line U251; even more, potent than that expressed by cisplatin. The <b>Cu2</b> showed remarkable potential to inhibit HeLa and HCT 116 cell line viability. Deeper insight into the mechanism underlying the cytotoxic effect suggested the involvement of the intrinsic pathway of apoptosis. Compound <b>Cu2</b> demonstrates more substantial pro-apoptotic effects, including more robust activation of <b>CASP3</b> and <b>BAX</b> proteins, while <b>Cu1</b> shows better interaction with <b>BCL2</b>. The interactions of the complex <b>Cu1</b> with bovine serum albumin BSA were studied to evaluate the mode of binding activities toward this biomolecule. The predicted drug-like properties and pharmacokinetics have revealed good absorption potential after oral administration.