Two Cu(II) complexes containing 2,4-diamino-6-(2-pyridy1)-1,3,5-triazine and amino acids: Synthesis, crystal structures, DNA/HSA binding, molecular docking, and in vitro cytotoxicity studies

Two new copper(II)-amino acid complexes, [Cu(PyTA)(L-Thr)(ClO4)](2) 1.5H(2)O (1) and [Cu(PyTA)(L-Arg) (ClO4)(H2O)] ClO4 (2) (PyTA = 2,4-diamino-6-(2-pyridyl)-1,3,5-triazine, L-Thr = L-threonine, L-Arg = L-arginine), were successfully synthesized and characterized. The results determined by single crystal X-ray diffraction showed that the five-coordinated copper of 1 and the six-coordinated copper of 2 were located in the distorted square-pyramidal and distorted octahedral environments, respectively. Spectroscopic titrations, thermal denaturation experiments, viscosity measurements revealed that the complexes bound to DNA via a groove binding mode, with the DNA-binding constants of 6.126 x 10(4)M(-1) for 1 and 6.464 x 10(4) M-1 for 2. Electrophoresis experiments revealed that the complexes cleaved pBR322 DNA by an oxidative pathway involving in the generation of superoxide free radical (O-2(-). Multi-spectroscopic analyses showed that the complexes bound to site I of human serum albumin (HSA) with moderate affinities. In particular, in vitro cytotoxicities of the complexes against Bel-7402 cell line showed promising anticancer effects (IC50 = 42.1 +/- 1.7 mu M for 1; IC50 = 36.3 +/- 0.9 mu M for 2). In addition, the binding mechanism and mode of the complexes with DNA/HSA were verified by molecular docking technique. (C) 2017 Elsevier B.V. All rights reserved.