Novel Cu 2+ and Zn 2+ nanocomplexes drug based on hydrazone ligand bearings chromone and triazine moieties: Structural, spectral, DFT, molecular docking and cytotoxic studies

Abstract

The bioactive 6-methyl-4-{{( E )-(4-oxo-4- H -chromen-3-yl)methylidene]amino-3-thioxo-3,4-dihydro-1,2,4- triazin-5(2 H )-one ( HL ) and its Cu 2+ and Zn 2 + complexes have been synthesized in nano-scale. The struc- ture and coordination behavior of HL ligand and its nanocomplexes have been investigated by various fundamental tools such as elemental and thermal analyses, molar conductivity and magnetic moment measurements. Also, FT-IR, 1 H NMR, mass, ESR and UV–Vis spectroscopy were recorded. The results cleared that forming mono-species of chelates with octahedral geometry, also the chelation may be oc- curred through N, O, S donor sites of the neutral ligand. TEM analysis showed that Cu 2+ complex has nano-rode morphology. On the other hand, the morphology of Zn 2+ complex has sheet with irregular shape within nano-domain. The hydrazone ( HL ) and its nanocomplexes were tested for their in vitro cytotoxicity against human Hepatocellular carcinoma cell line (HepG-2). The Cu 2+ nanocomplex showed highly inhibition against HepG-2 growth (IC 50 = 0.027 μM) with respect to the prepared compounds and different standard drugs. The high antitumor activity of Cu 2+ nanocomplex was discussed with respect to its chemical structure, Cu 2+ reducing capacity and nano size character. Furthermore, computational studies of the ligand ( HL ) and its nanocomplexes were estimated using DFT method. From the optimized struc- ture, different chemical quantum parameters were calculated. Docking studies were used to investigate the interaction between HL and its nanocomplexes with the active site of the CDK2 kinase.