New salen-type manganese(III) Schiff base complexes derived from meso-1,2-diphenyl-1,2-ethylenediamine: In vitro anticancer activity, mechanism of action, and molecular docking studies

Four new manganese(III) Schiff base complexes (1-4) were synthesized and characterized. The complexes have general formula [MnClLx] in which L represents a Schiff base ligand derived from condensation of meso-1,2-diphenyl-1,2-ethylenediamine with salicylaldehyde or its 3-OMe-, 5-Br-, or 5-OMe-derivatives (x=1-4, respectively). The crystal structure of [MnClL1] (1) was characterized by X-ray crystallography. The in vitro anticancer activity of these complexes was evaluated by MTT and apoptosis assays against human breast (MCF-7) and liver (Hep G2) cancer cells. The complexes exhibited considerable antiproliferative activity against both cell lines (IC50=10.8-21.02M) comparable to cis-platin, except 4 (MCF-7). The highest activity was found for 1 with IC50 values of 13.62M (MCF-7) and 10.8M (Hep G2). Flow cytometry experiments showed that 1 induced apoptosis on MCF-7 tumor cell line. Docking simulations using AUTODOCK were also carried out. The results showed that all complexes fitted into the minor groove region of DNA.