New Mn(III)/Fe(III) complexes with thiohydantoin-supported imidazolium ionic liquids for breast cancer therapy

Abstract

This study offers, for the first time, the design and synthesis of hybrids integrating imidazolium ionic liquids (IMILs) and thiohydantoins (THs) motifs and their Mn/Fe(III) complexes for cancer therapeutic applications. The molecular structures of thiohydantoin-supported imidazolium ionic liquids (THIMILs) (4a-c) and their complexes were proposed based on microanalytical and spectroscopic investigations. On the other hand, the UV–Vis spectroscopic and magnetic measurements, as well as comparisons with previously reported comparable complexes, led to the postulation of square pyramidal and octahedral geometries for Mn(III)THIMIL and Fe(III)THIMIL complexes, respectively. According to the MTT cytotoxicity assay results, the new hybrids inhibited MCF-7 cell proliferation more effectively than HepG2 and selectively as well. The anti-breast cancer performance varies depending on the hybrid structure, dose, and treatment duration. Among the compounds tested, Fe(III)THIMIL analog (6b) was the most active and selective anti-MCF-7 agent (IC50 1.98±0.56 μM, SI 34.92). It was found that 6b has the capacity to trigger G2/M cell cycle arrest and apoptosis in MCF-7 cells, presumably through a p50 route. Meanwhile, the molecular docking of 6b with Bcl-2 and p50 proteins showed great promise in the field of cancer treatment by modulating the levels of expression in these proteins.