Anticancer activities of a β-amino alcohol ligand and nanoparticles of its copper(<scp>ii</scp>) and zinc(<scp>ii</scp>) complexes evaluated by experimental and theoretical methods

Abstract

2-(2-(2-Hydroxyethylamino)ethylamino)cyclohexanol (HEAC) and copper and zinc complexes, [Cu(HEAC)Cl]Cl (1), [Cu(HEAC)Br]Br (2), [Zn(HEAC)Cl₂] (3), were prepared and identified by elemental analysis, FT-IR, UV-Vis, ¹H NMR spectroscopy and single-crystal X-ray diffraction. Also nanoparticles of 1-3 were prepared for anticancer studies by ultrasonic irradiation. Particle size and morphology of the nano particles are investigated by PXRD and SEM, respectively. X-ray analysis revealed that the ionic complexes 1 and 2 are isostructural. In the structure of complexes 1 and 2, the metal atom has a CuN₂O₂X (X: Cl (1), Br (2)) environment with square-pyramidal geometry, containing the tetradentate N₂O₂-donor HEAC. The bond length of the axial position in the square-pyramidal geometry of 1 and 2 is elongated. Complex 3 has a ZnN₂OCl₂ environment with trigonal bipyramidal geometry around the zinc atom in which the HEAC acts as <i>mer</i>-N₂O-donor. The ability of HEAC and nano particles 1-3 to interact with the nine biomacromolecules (BRAF kinase, CatB, DNA gyrase, HDAC7, rHA, RNR, TrxR, TS and Top II) are investigated by docking calculations. For examination of the docking results, the <i>in vitro</i> activities of four compounds against the human leukemia cell line K562 were investigated by evaluation of IC₅₀ values and mode of cell death (apoptosis). The thermodynamic stability of the compounds along with the charge distribution pattern were studied by DFT and NBO analysis, respectively.