Fabrication, DFT Calculation, and Molecular Docking of Two Fe(III) Imine Chelates as Anti-COVID-19 and Pharmaceutical Drug Candidate.

ABSTRACT

Two tetradentate dibasic chelating Schiff base iron (III) chelates were prepared from the reaction of 2,2'-((1E,1'E)-(1,2-phenylenebis(azanylylidene))bis(methanylylidene))bis(4-bromophenol) (PDBS) and 2,2'-((1E,1'E)-((4-chloro-1,2-phenylene)bis(azanylylidene))-bis(methanylylidene))bis(4-bromophenol) (CPBS) with Fe3+ ions. The prepared complexes were fully characterized with spectral and physicochemical tools such as IR, NMR, CHN analysis, TGA, UV-visible spectra, and magnetic moment measurements. Moreover, geometry optimizations for the synthesized ligands and complexes were conducted using the Gaussian09 program through the DFT approach, to find the best structures and key parameters. The prepared compounds were tested as antimicrobial agents against selected strains of bacteria and fungi. The results suggests that the CPBSFe complex has the highest activity, which is close to the reference. An MTT assay was used to screen the newly synthesized compounds against a variety of cell lines, including colon cancer cells, hepatic cellular carcinoma cells, and breast carcinoma cells. The results are expressed by IC50 value, in which the 48 µg/mL value of the CPBSFe complex indicates its success as a potential anticancer agent. The antioxidant behavior of the two imine chelates was studied by DPPH assay. All the tested imine complexes show potent antioxidant activity compared to the standard Vitamin C. Furthermore, the in vitro assay and the mechanism of binding and interaction efficiency of the tested samples with the receptor of COVID-19 core protease viral protein (PDB ID 6lu7) and the receptor of Gram-negative bacteria (Escherichia coli, PDB ID 1fj4) were investigated using molecular docking experiments.