Bis(imidazol-1-yl)methane-based heteroscorpionate metal(II) complexes: Theoretical, antimicrobial, antioxidant, in vitro cytotoxicity and c-Met tyrosine kinase studies

Abstract

The C-centered bis(imidazol-1-yl)methane-based heteroscorpionate metal(II) complexes of the type [M(L1−3)Cl] (1–9), where M = Mn(II), Ni(II) or Cu(II) have been synthesized using the heteroscorpionate ligands, (2-hydroxyphenyl)bis(imidazol-1-yl)methane (HL1), (4-diethylamino-2-hydroxyphenyl)bis(imidazol-1-yl)methane (HL2) and (5-bromo-2-hydroxyphenyl)bis(imidazol-1-yl)methane (HL3). The spectral and theoretical studies suggested tetrahedral geometry for manganese(II) and nickel(II) complexes, and square-planar geometry for copper(II) complexes. The antimicrobial activity of the complexes was evaluated against two Gram (–ve) (Shigella dysenteriae and Vibrio cholerae) and two Gram (+ve) (Bacillus cereus and Streptococcus faecalis) bacterial, and three fungal (Candida albicans, Candida glabrata and Candida krusei) strains. The antioxidant activity of the ligands and their nickel(II) and copper(II) complexes were determined by ABTS, DPPH and H2O2 free radical scavenging assays. In vitro cytotoxicity activity of the ligands and their nickel(II) and copper(II) complexes were tested against human breast adenocarcinoma (MCF-7), cervical (HeLa) and lung (A549) cancerous and normal human dermal fibroblast (NHDF) cell lines by MTT reduction assay. The copper(II) complex 8 exhibit higher cytotoxicity activity than the other complexes against all the tested cancer cell lines. Molecular docking studies of the complexes were also performed with c-Met tyrosine kinase receptor to determine the possible binding mode and predominant binding interactions.