N2O2‐chelate metal complexes with Schiff base ligand: Synthesis, characterisation and contribution as a promising antiviral agent against human cytomegalovirus

Abstract

A new Schiff base, (N,N\‐phenylene‐(bis‐1‐ethyl‐6‐fluoro‐7‐(piperazine‐1‐yl)‐quinolone‐3‐carboxylic acid) and (Nor‐o‐phdn.2H2O), and its derived complexes with nickel (II), cobalt (II), copper (II), iron (III), yttrium (III), lanthanum (III), zirconium (IV) and uranium (VI) were synthesised and distinguished by different tools such as elemental analyses, magnetic properties, molar conductivity, spectroscopic methods (UV‐Vis., IR and1H‐NMR), mass spectrometry and thermogravimetric analysis. Depending on the spectroscopic data, Schiff base Nor‐o‐phdn.2H2O is coordinated to metal centres as a potentially tetradentate ligand via N2O2atoms. UV‐Vis. and magnetic data suggest an octahedral‐geometry for all mentioned complexes. Thermogravimetric analysis indicated the existence of water molecules inside and outside complex sphere. The thermodynamics‐related parameters were analysed through using Horowitz–Metzger and Coats–Redfern formula. Schiff base as well as its metal‐derived complexes were assessed for their antibacterial, antifungal and antiviral bioactivities. As anticipated, Schiff base and its metal complexes showed high antibacterial profile againstEscherichia coliandSalmonellatyphi. In case ofStaphylococcus aureusandBacillus cereus, it was observed that metal‐derived complexes exhibited more bactericidal features than the uncomplexed ligands. However, there are no antifungal bioactivities detected. Regarding the antiviral bioactivity, we determined in an innovative manner the effectiveness of Schiff base and metal‐derived complexes on the replication of human cytomegalovirus (huCMV‐DNA). In this regard, we utilised a humanised mouse model (huNOG‐EXL) that was implanted with human immune system cells and was subsequently infected with huCMV. The infected mice divided into drug‐treated mice and the drug‐untreated vehicle control. After postinfection and during the course of treatment, Fe (III) and Zr (IV) complexes were impactful in obstructing huCMV replication by 10‐15 fold when compared with the vehicle control, concomitantly with inducing the immune recognition of T‐cytotoxic CD8+cells towards the huCMV. The complexes are believed to be the best nominees for further research and development as huCMV inhibitors.