Two Cu(II) complexes containing 2,4-diamino-6-(2-pyridyl)-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)(ClO 4 )] 2 ·1.5H 2 O ( 1 ) and [Cu(PyTA)( l -Arg)(ClO 4 )(H 2 O)]·ClO 4 ( 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 × 10 4 M −1 for 1 and 6.464 × 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 (IC 50 = 42.1 ± 1.7 μM for 1 ; IC 50 = 36.3 ± 0.9 μM for 2 ). In addition, the binding mechanism and mode of the complexes with DNA/HSA were verified by molecular docking technique. [ABSTRACT FROM AUTHOR]