A new Cu(II) complex derived from the reaction between tris(2-aminoethyl)amine and Cu(I)-activated acetonitrile with potent anticancer activity against some cell lines and high affinity for the essential proteins of SARS-CoV-2

In this project a water-soluble Cu(II) complex, [CuL]Cl<middle dot>H2O (L = N){(CH2CH2N=C(CH3)NH2)(2)(CH2CH2N=C(CH3)NHCOO-)}, was synthesized through an amidation-oxidation reaction between Cu(I) ions, tris(2-aminoethyl)amine (tren), CH3CN and CO2 molecules in acetonitrile-methanol solution. The above complex was characterized using FT-IR, CHN analysis and by single crystal X-ray structure determination. The structural analysis shows that the tertiary nitrogen atom, three imine nitrogen atoms of the amidine groups and one oxygen atom of the anionic terminal carbamate group of the ligand are all coordinated to the central Cu(II) ion. The DNA interaction studies of the complex with calf thymus DNA (ct-DNA) were carried out using viscosity measurements, UV-Vis and competitive fluorescence spectroscopies and molecular docking simulations. All the above experimental measurements in solution as well as the docking simulations showed that the above complex binds to DNA via a minor groove binding mode. Also, the anticancer activity of the complex against MCF-7, CT-26 and normal HEK-293 cell lines were evaluated and compared with cisplatin (CP) as a reference anticancer drug. The results showed that the toxicity caused by the complex in all of cells is comparable to CP. Furthermore, the affinity of the complex for the essential proteins of the SARS-CoV-2 virus was also simulated. The obtained binding affinity values by Vina indicated that the complex has favorable binding affinity when compared to favipiravir, hydroxychloroquine and remdesivir, all potent anti-COVID-19 agents.