Synthesis and characterization of two new mixed-ligand Cu(II) complexes of a tridentate NN'O type Schiff base ligand and N-donor heterocyclic co-ligands: In vitro anticancer assay, DNA/human leukemia/COVID-19 molecular docking studies, and pharmacophore modeling.

Two new mixed-ligand complexes with general formula [Cu(SB)(L')]ClO 4 ( 1 and 2 ) were synthesized and characterized by different spectroscopic and analytical techniques including Fourier transform infrared (FT-IR) and UV-Vis spectroscopy and elemental analyses. The SB ligand is an unsymmetrical tridentate NN'O type Schiff base ligand that was derived from the condensation of 1,2-ethylenediamine and 5-bromo-2-hydroxy-3-nitrobenzaldehyde. The L' ligand is pyridine in ( 1 ) and 2,2'-dimethyl-4,4'-bithiazole ( BTZ ) in ( 2 ). Crystal structure of ( 2 ) was also obtained. The two complexes were used as anticancer agents against leukemia cancer cell line HL-60 and showed considerable anticancer activity. The anticancer activity of these complexes was comparable with the standard drug 5-fluorouracil (5-FU). Molecular docking and pharmacophore studies were also performed on DNA (PDB:1BNA) and leukemia inhibitor factor (LIF) (PDB:1EMR) to further investigate the anticancer and anti-COVID activity of these complexes. The molecular docking results against DNA revealed that ( 1 ) preferentially binds to the major groove of DNA receptor whereas ( 2 ) binds to the minor groove. Complex ( 2 ) performed better with 1EMR. The experimental and theoretical results showed good correlation. Molecular docking and pharmacophore studies were also applied to study the interactions between the synthesized complexes and SARS-CoV-2 virus receptor protein (PDB ID:6LU7). The results revealed that complex ( 2 ) had better interaction than ( 1 ), the free ligands ( SB and BTZ ), and the standard drug favipiravir.