Monosaccharide Linked Schiff Base Metal Complexes of Cu(II), Zn(II) and Mn(II): Exploring the Antiproliferative Activity and Cell Death Mechanism

Abstract

Herein, a new type of Schiff base ligand, HSL2 (where HSL2=2,2,7,7‐tetramethyltetrahydro‐3aH‐bis[1,3]dioxolo[4,5‐b:4′,5′‐d]pyran‐5‐yl) methyl‐4‐(3,5‐dichloro‐2‐hydroxybenzylidene amino)benzoate) anchored with a monosaccharide unit have been synthesized and characterized by FT‐IR, 1H NMR, and ESI‐MS. The ligand are chelated to metal ions Zn(II) (1), Cu(II) (2), and Mn(II) (3) to from square planar/tetrahedral or octahedral complexes. The DFT studies are carried out to optimize the shapes of the compounds. Moreover, Cu(II) and Mn(II) complexes were also characterized by EPR spectroscopy. The cytotoxicity of the complexes was screened towards three different cell lines A549 (lung cancer), HeLa (cervical cancer), and HT29 (colorectal cancer). These complexes exhibited significant cytotoxicity against three aforementioned cell lines and IC50 values are found in the range of 19.77–23 μM on HeLa cells, 9.42–12.25 μM on A549 cells and 8.84–16 μM on HT29 cells. The cell death mechanism was also studied by employing DNA fragmentation, Hoechst 33342 nuclear staining, and Acridine orange/ Ethidium Bromide (AO/EB) assay. In addition, ROS generation was also evaluated with these metal complexes.