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

<jats:title>Abstract</jats:title><jats:p>Two new mixed‐ligand complexes with general formula [Cu(SB)(L')]ClO<jats:sub>4</jats:sub> (<jats:bold>1</jats:bold> and <jats:bold>2</jats:bold>) 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 (<jats:bold>1</jats:bold>) and 2,2′‐dimethyl‐4,4′‐bithiazole (<jats:bold>BTZ</jats:bold>) in (<jats:bold>2</jats:bold>). Crystal structure of (<jats:bold>2</jats:bold>) 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 (<jats:bold>1</jats:bold>) preferentially binds to the major groove of DNA receptor whereas (<jats:bold>2</jats:bold>) binds to the minor groove. Complex (<jats:bold>2</jats:bold>) 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 (<jats:bold>2</jats:bold>) had better interaction than (<jats:bold>1</jats:bold>), the free ligands (<jats:bold>SB</jats:bold> and <jats:bold>BTZ</jats:bold>), and the standard drug favipiravir.</jats:p>